Diagnostic value of multiple b-value diffusion-weighted imaging in discriminating the malignant from benign breast lesions.

OBJECTIVE: The conventional breast Diffusion-weighted imaging (DWI) was subtly influenced by microcirculation owing to the insufficient selection of the b values. However, the multiparameter derived from multiple b-value exhibits more reliable image quality and maximize the diagnostic accuracy. We aim to evaluate the diagnostic performance of stand-alone parameter or in combination with multiparameter derived from multiple b-value DWI in differentiating malignant from benign breast lesions. METHODS: A total of forty-one patients diagnosed with benign breast tumor and thirty-eight patients with malignant breast tumor underwent DWI using thirteen b values and other MRI functional sequence at 3.0 T magnetic resonance. Data were accepted mono-exponential, bi-exponential, stretched-exponential, aquaporins (AQP) model analysis. A receiver operating characteristic curve (ROC) was used to evaluate the diagnostic performance of quantitative parameter or multiparametric combination. The Youden index, sensitivity and specificity were used to assess the optimal diagnostic model. T-test, logistic regression analysis, and Z-test were used. P value < 0.05 was considered statistically significant. RESULT: The ADCavg, ADCmax, f, and α value of the malignant group were lower than the benign group, while the ADCfast value was higher instead. The ADCmin, ADCslow, DDC and ADCAQP showed no statistical significance. The combination (ADCavg-ADCfast) yielded the largest area under curve (AUC = 0.807) with sensitivity (68.42%), specificity (87.8%) and highest Youden index, indicating that multiparametric combination (ADCavg-ADCfast) was validated to be a useful model in differentiating the benign from breast malignant lesion. CONCLUSION: The current study based on the multiple b-value diffusion model demonstrated quantitatively multiparametric combination (ADCavg-ADCfast) exhibited the optimal diagnostic efficacy to differentiate malignant from benign breast lesions, suggesting that multiparameter would be a promising non-invasiveness to diagnose breast lesions.

Comparative proteomic analysis of Leptospira interrogans serogroup Icterohaemorrhagiae human vaccine strain and epidemic isolate from China.

Leptospira interrogans serogroup Icterohaemorrhagiae is the predominant pathogen causing leptospirosis in China and is still used as the vaccine strain for the current human inactivated vaccine. Unlike the clade ST17, which is distributed worldwide, ST1 is the most prevalent in serogroup Icterohaemorrhagiae in China. To further characterize leptospiral pathogens, isobaric tags for relative and absolute quantitation and parallel reaction monitoring were used to analyze differences at the proteomic level between serogroup Icterohaemorrhagiae vaccine strain 56001 (ST1) and circulating isolate 200502 (ST17) from different periods. Two hundred and eighty-one proteins were differentially expressed between the circulating isolate and vaccine strain, of which 166 were upregulated (> 1.2-fold change, P < 0.05) and 115 (< 0.8-fold change, P < 0.05) were downregulated. Function prediction revealed that nine upregulated proteins were outer membrane proteins, including several known immunogenic and/or virulence-related proteins, such as ompL1, LipL71, and LipL41. Furthermore, important expression differences in carbohydrate, amino acid, and energy metabolism and transport proteins were identified between both strains from different clusters, suggesting that these differences may reflect metabolic diversity and the potential of the pathogens to adapt to different environments. In summary, our findings provide insights into a better understanding of the component strains of the Chinese human leptospirosis vaccine at the proteomic level. Additionally, these data facilitate evaluating the mechanisms by which pathogenic Leptospira species adapt to the host environment.

Evaluation of liver function in patients with chronic hepatitis B using Gd-EOB-DTPA-enhanced T1 mapping at different acquisition time points: a feasibility study.

PURPOSE: This study aimed to explore the impact of different acquisition times on the evaluation of liver function levels in chronic hepatitis B using Gd-EOB-DTPA-enhanced T1 positioning technology under 3.0 Tesla magnetic resonance imaging (MRI). METHODS: A total of 146 patients with chronic hepatitis B (CHB) were classified into four groups as follows: chronic hepatitis B without liver cirrhosis (CH, 22 cases), liver cirrhosis with Child-Pugh classification A (LCA 63 cases), Child-Pugh B (LCB 47 cases) and Child-Pugh C (LCC 14 cases). Normal liver function (NLF) group was composed of 23 persons who had healthy liver and no medical histories of hepatitis. T1 mapping images were performed before and after administration of Gd-EOB-DPTA using Look-Locker sequence. Changes in T1 relaxation time (T1rt), the reduction rate of T1 relaxation time (ΔT1) and the increase in T1 relaxation rate (ΔR1) of liver over time (at 5, 10, 15 and 20 min) were investigated and compared among all five groups using a one-way analysis of variance (ANOVA). The Spearman's rank correlation coefficient (r) was used to show the correlations of these parameters in different liver function groups. RESULTS: In the NLF, CH, LCA and LCB groups, postT1 gradually decreased, while the ΔT1 and ΔR1 gradually increased with time. The parameters were compared between different liver function levels at the same time point, and the differences were statistically significant except for NLF-CH, NLF-LCA and CH-LCA. There was no significant difference in the area under the ROC curve of other parameters at 10, 15 and 20 min. At each time point, no correlation was found between preT1rt and the degrees of liver function. PostT1rt was positively correlated with liver function classification, while ΔT1 and ΔR1 were negatively correlated with liver function classification. CONCLUSION: Gd-EOB-DTPA-enhanced T1 mapping magnetic resonance imaging is beneficial to assess liver function. Using the Gd-EOB-DTPA to enhance T1 mapping imaging to assess liver function can shorten the observation time of the hepatobiliary period and 10 min after enhancement may be the best time point.

Evaluation of a beneficial effect of adjuvant chemotherapy in patients with stage I triple-negative breast cancer: a population-based study using the SEER 18 database.

PURPOSE: To evaluate the effect of adjuvant chemotherapy on improving the prognosis of patients with stage I triple-negative breast cancer (TNBC). METHODS: TNBC patients diagnosed in the SEER 18 database from 2010 to 2015 were included. Kaplan-Meier plots and log-rank tests were used to compare the differences in breast cancer-specific survival (BCSS) and overall survival (OS) between subgroups of variables. A Cox proportional hazard model was used to determine the prognostic factors affecting BCSS and OS. RESULTS: A total of 9256 patients were enrolled in this study. Among these patients, 380 died from breast cancer, and 703 died from all causes. Patients who received chemotherapy had significantly better BCSS and OS than those who did not receive chemotherapy for stage T1cN0M0 (BCSS, hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.51-0.90; OS, HR = 0.54, 95% CI 0.44-0.67) and stage IB (BCSS, HR = 0.39, 95% CI 0.16-0.95; OS, HR = 0.41, 95% CI 0.19-0.87) disease. Patients who received chemotherapy did not have significantly better BCSS or OS than those who did not receive chemotherapy for stage T1aN0M0 or T1bN0M0 disease. The patients who received chemotherapy in the poorly differentiated and undifferentiated groups had better BCSS (HR = 0.68, 95% CI 0.52-0.88) and OS (HR = 0.54, 95% CI 0.44-0.66) than the patients who did not receive chemotherapy. CONCLUSION: According to current clinical guidelines, patients with stage T1bN0M0 TNBC are probably overtreated. The prognosis of these patients with stage T1aN0M0 or T1bN0M0 disease is good enough that adjuvant chemotherapy cannot improve it further.

Long-term biological variation estimates of 13 hematological parameters in healthy Chinese subjects.

Background The complete blood count (CBC) is a basic test routinely ordered by physicians as a part of initial diagnostic work-up on their patients. To ensure safe clinical application of the CBC, reliable biological variation (BV) data are needed to establish analytical performance specifications. Our aim was to define the BV of CBC parameters using a rigorous protocol that is compliant with the Biological Variation Data Critical Appraisal Checklist (BIVAC) provided by the European Federation of Clinical Chemistry and Laboratory Medicine. Methods Blood samples drawn from 41 healthy Chinese subjects (22 females and 19 males; 23-59 years of age) once monthly for 6 consecutive months were analyzed using an ABX Pentra 80 instrument. The instrument was precisely calibrated. All samples were analyzed in duplicate for 13 CBC parameters. The data were assessed for outliers, normality, and variance homogeneity prior to nested ANOVA. Gender-stratified within-subject (CVI) and between-subject (CVG) BV estimates were calculated. Results The number of remaining data for each subject was 442-484 after removing outliers. No significant differences existed between female/male CVI estimates. Except for leukocytes, neutrophils, and lymphocytes, the mean values of 10 parameters differed significantly between genders, rendering partitioning of CVG data between genders. No significant differences were detected between most BV estimates and recently published estimates representing a Europid population. Conclusions Most BV estimates in BIVAC-compliant studies are similar. The turnover time of blood cells and age distribution of participants should be considered in a CBC BV study. Our study will contribute to global BV estimates and future studies.

Study of total error specifications of lymphocyte subsets enumeration using China National EQAS data and Biological Variation Data Critical Appraisal Checklist (BIVAC)-compliant publications.

Objectives: It is important to select proper quality specifications for laboratories and external quality assessment (EQA) providers for their quality control and assessment. The aim of this study is to produce new total error (TE) specifications for lymphocyte subset enumeration by analyzing the allowable TE using EQAS data and comparing them with that based on reliable biological variation (BV). Methods: A total of 54,400 results from 1,716 laboratories were collected from China National EQAS for lymphocyte subset enumeration during the period 2017-2019. The EQA data were grouped according to lower limits of reference intervals for establishing concentration-dependent specifications. The TE value that 80% of laboratories can achieve were considered as TE specifications based on state of the art. The BV studies compliant with Biological Variation Data Critical Appraisal Checklist (BIVAC) were used to calculate the three levels of TE specifications. Then these TE specifications were compared for determining the recommended TE specifications. Results: Four parameters whose quality specifications could achieve the optimum criteria were as follows: the percentages of CD3+, CD3+CD4+ (high concentration) and CD3-CD16/56+ cells, and the absolute count of CD3-CD16/56+ cells. Only the TE specifications of CD3-CD19+ cells could achieve the minimum criteria. The TE specifications of remaining parameters should reach the desirable criteria. Conclusions: New TE specifications were established by combining the EQA data and reliable BV data, which could help laboratories to apply proper criteria for continuous improvement of quality control, and EQA providers to use robust acceptance limits for better evaluation of EQAS results.

[Genetic variation in SDC2 is associated with the risk of radiation esophagitis in patients with esophageal squamous cell carcinoma receiving radiotherapy].

OBJECTIVE: To explore the associations between the genetic variations in the SDC2 gene and overall survival and risk of radiation esophagitis in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Eleven functional haplotype-tagging single nucleotide polymorphisms (htSNPs) of SDC2 were genotyped in 296 ESCC patients who received radiotherapy alone, and had different response and esophagitis. The associations between genotypes and risk of esophagitis were measured by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for sex, age, tumor location, staging, radiotherapy mode and total radiation dose. The hazard ratios (HRs) were estimated using Cox proportional hazards regression model. RESULTS: The median survival time (MST) of these patients was 14 months. Of them, 260 (87.8%) had died until the last date of follow-up of 30 June, 2014. Clinical stage (stage IV vs. stage II) and total radiation dose (≥ 60 Gy vs. < 60 Gy) influence the overall survival time of the patient significantly. Cox proportional hazards regression model analysis showed that the subjects with rs61599409 T allele had an decreased hazard ratio as compared with those with C allele (adjusted HR = 0.82, 95% CI, 0.66-1.02), but the difference was not statistically significant (P = 0.071). The rest 10 htSNPs were not associated with the overall survival of ESCC patients treated with radiotherapy. Among this set of patients, 160 (54.1%) suffered from radiation esophagitis. We found that rs17788084 A > T SNP in the 3'-untranslational region of SDC2 was associated with esophagitis risk, with the OR being 0.48 (95% CI = 0.28-0.85, P = 0.011) for the TA or TT genotype compared with the AA genotype. CONCLUSIONS: These results suggest that rs17788084 genetic variation in SDC2 is associated with risk of radiation esophagitis and might serve as a potential biomarker for personalized radiotherapy of ESCC.

[A preliminary study of dual-source computed tomography dual energy imaging in the diagnosis of acute traumatic bone marrow lesions in spine].

OBJECTIVE: To explore the feasibility of virtual noncalcium technique from dual-source computed tomography (DSCT) for the diagnosis of vertebral bone marrow lesions. METHODS: A total of 13 patients with acute vertebral bone marrow lesions underwent both DSCT and MRI within 3 days. And the DSCT dual-energy CT data were postprocessed for generating virtual noncalcium images and color-coded maps. Two radiologists analyzed the lesions of bone marrow by magnetic resonance (MR) imaging and virtual noncalcium images on a three-level. MR imaging interpretation served as the reference standard. Consistency check was conducted by using kappa statistics. And then the sensitivity of DSCT dual energy imaging was examined in the diagnosis of acute traumatic bone marrow lesions in spine. RESULTS: Among them, 13 vertebral body with bone marrow lesions were detected by MRI. The T2WI fat-suppression irregular high signal and slightly high density shadow under the background in noncalcium images corresponded to corresponding high signal areas on MRI. Interreader agreement was substantial for qualitative grading of DE CT images (κ = 0.629). The sensitivity of DSCT dual energy virtual noncalcium images in the diagnosis of acute traumatic bone marrow lesions in spine were 92.3% and 84.6% for observers 1 and 2. CONCLUSION: Distinct traumatic bone marrow lesions of spine may be diagnosed with a high sensitivity on virtual noncalcium images reconstructed from DSCT and color-coded maps. And it is worth further explorations.

Coagulation factors VIII and factors IX testing practices in China: Results of the 5-year external quality assessment program.

BACKGROUND AND AIMS: Testing for coagulation factors VIII (FVIII) and IX (FIX) plays significant importance in the diagnostic and treatment of hemophilia A and B. External quality assessment (EQA) scheme aimed to assess the participants' performance of testing for coagulation factors and identify shortcomings in clinical practice. This study aimed to investigate the performance trends of the participating laboratories in China national external quality assessment Scheme (China NEQAS) for FVIII and FIX over a five-year period (2019-2023). MATERIALS AND METHODS: A total of ten external quality assessment (EQA) rounds were conducted from 2019 to 2023 in the China NEQAS for FVIII and FIX. The distribution of method, reagent and instrument were calculated. The trends of method- specific inter-laboratory coefficient of variation (CV) and pass rates were analyzed over 5 years. The dilutions for coagulation factor testing were also investigated. RESULTS: All laboratories use one-stage assays to detect FVIII and FIX activity. The inter-laboratory overall CV decreased year by year (10.9 % to 9.3 % for FVIII and 13.5 % to 10.2 % for FIX), and the laboratory pass rate steadily increased (88.0 % to 93.4 % for FVIII and 81.3 % to 92.7 % for FIX). The majority of laboratories employed a single dilution methodology for the assessment of FVIII and FIX activity. The interlaboratory CV was elevated for the Siemens reagent (Actin FSL) during analysis of moderately abnormal FIX concentrations of EQA samples in most batches. CONCLUSIONS: The implementation of the external quality assessment has contributed to facilitate the enhancement of testing quality. Chromogenic assay is a supplement to accurate determination when necessary. Laboratories may choose to perform dilution tests or direct assays to identify the presence of inhibitors, particularly when they are suspected.

[Impact of CCND1 A870G polymorphism on acute adverse events in postoperative rectal cancer patients treated with adjuvant concurrent chemoradiotherapy].

OBJECTIVE: The purpose of this study was to investigate the association between single nucleotide polymorphism (SNP) of CCND1 A870G and acute adverse events (AEs) in postoperative rectal cancer patients who received capecitabine-based postoperative chemoradiotherapy (CRT). METHODS: Four hundred patients with stage II and III rectal cancer received postoperative CRT of capecitabine with or without oxaliplatin were accumulated and prostectively studied in this study. The patients were randomly divided into two groups. Two hundred and twenty-eight patients were treated with concurrent capecitabine and radiotherapy (Cap-CRT), and 172 patients were treated with capecitabine and oxaliplatin plus radiotherapy (Cap-Oxa-CRT). Adverse events were graded according to the Common Terminology Criteria for Adverse Events, v. 3.0 (CTCAE v3.0). The genotype of CCND1 A870G in the patients was detected by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. The associations between the SNP and acute AEs were indicated by odds ratios (ORs) and 95% confidence intervals (CIs), which were computed with logistic regression model. RESULTS: A total of 136 patients presented severe AEs. Among them the frequencies of the three genotypes GG, GA and AA were 16.9%, 50.7% and 32.4%, compared with 24.6%, 48.1% and 27.3%, respectively, among the patients without severe AEs. Diarrhea was the most common AE, and severe diarrhea occurred in 109 patients. The frequencies of the three genotypes GG, GA and AA were 15.6%, 47.7% and 36.7% among these patients, compared with 24.4%, 49.5% and 26.1%, respectively, among patients without severe diarrhea. Multivariate logistic regression analysis showed a 1.66-fold increased risk for severe diarrhea in patients with AA genotype (95%CI 1.03 - 2.67, P = 0.038) compared with the cases with GG or GA genotypes. Stratified analysis showed that in the Cap-Oxa-CRT group, patients with AA genotype showed a 2.34-fold increased risk for severe diarrhea (95%CI 1.16 - 4.76, P = 0.018) compared with those with GG or GA genotypes, but in the Cap-CRT group, the SNP was not associated with the risk of severe diarrhea. CONCLUSIONS: The genetic polymorphism of CCND1 A870G might be a potential biomarker for predicting acute AEs in postoperative stage II and III rectal cancer patients treated with adjuvant concurrent chemoradiotherapy of capecitabine and oxaliplatin.

Two Novel Intronic Mutations in the CSF1R Gene in Two Families With CSF1R-Microglial Encephalopathy.

Objective: To describe two novel heterozygous splicing variants of the CSF1R gene responsible for CSF1R-microglial encephalopathy in two unrelated Han Chinese families and further explore the relationship between the pathological and neuroimaging findings in this disease. Methods: The demographic data, detailed medical history, and clinical manifestations of two unrelated Han families with CSF1R-microglial encephalopathy were recorded. Some family members also underwent detailed neuropsychological evaluation, neuroimaging, and genetic testing. The probands underwent whole-exome sequencing (WES) or next-generation sequencing (NGS) to confirm the diagnosis. The findings were substantiated using Sanger sequencing, segregation analysis, and phenotypic reevaluation. Results: Both families presented with a dominant hereditary pattern. Five of 27 individuals (four generations) from the first family, including the proband and his sister, father, uncle, and grandmother, presented with cognitive impairments clinically during their respective lifetimes. Brain magnetic resonance imaging (MRI) depicted symmetric, confluent, and diffuse deep white matter changes, atrophy of the frontoparietal lobes, and thinning of the corpus callosum. The proband's brother remained asymptomatic; brain MRI revealed minimal white matter changes, but pseudo-continuous arterial spin labeling (pCASL) demonstrated a marked reduction in the cerebral blood flow (CBF) in the bilateral deep white matter and corpus callosum. Seven family members underwent WES, which identified a novel splice-site heterozygous mutation (c.2319+1C>A) in intron 20 of the CSF1R gene in four members. The proband from the second family presented with significant cognitive impairment and indifference; brain MRI depicted symmetric diffuse deep white matter changes and thinning of the corpus callosum. The proband's mother reported herself to be asymptomatic, while neuropsychological evaluation suggested mild cognitive impairment, and brain MRI demonstrated abnormal signals in the bilateral deep white matter and corpus callosum. NGS of 55 genes related to hereditary leukodystrophy was performed for three members, which confirmed a novel splice-site heterozygous mutation (c.1858+5G>A) in intron 13 of the CSF1R gene in two members. Conclusions: Our study identified two novel splicing mutation sites in the CSF1R gene within two independent Chinese families with CSF1R-microglial encephalopathy, broadening the genetic spectrum of CSF1R-microglial encephalopathy and emphasizing the value of pCASL for early detection of this disease.

Downregulation of GSK3B by miR-132-3p Enhances Etoposide-Induced Breast Cancer Cell Apoptosis.

OBJECTIVE: MicroRNAs (miRNAs) have been confirmed to play an essential role in modulating cancer cell proliferation, metastasis, and sensitivity to chemotherapy. However, the correlation between miR-132-3p expression and etoposide (VP16) induced apoptosis in human breast cancer cells remains poorly understood. METHODS: Six datasets, including three gene expression profile datasets and three microRNA (miRNA) expression profile datasets, were downloaded from the NCBI Gene Expression Omnibus (GEO) database to identify miR-132-3p and GSK3B expression in breast cancer. Kaplan-Meier and log-rank testing were performed to evaluate the effect of miR-132-3p and GSK3B on the survival of breast cancer. Flow cytometry analysis was used to determine the effects of miR-132-3p and GSK3B on breast cancer cell apoptosis. Luciferase reporter assay, Western blot, and real-time PCR were used to determine the regulatory effect of miR-132-3p on GSK3B. RESULTS: miR-132-3p was significantly downregulated in breast cancer tissues compared with normal breast epithelial cells, whereas GSK3B expression was remarkably over-expressed in breast cancer tissues. The patients with low miR-132-3p or high GSK3B expression had worse overall survival. Luciferase reporter assay, Western blot, and real-time PCR confirmed that miR-132-3p could inhibit GSK3B protein and mRNA expression via binding to the 3'-UTR of GSK3B. Furthermore, miR-132-3p enhanced VP16-induced breast cancer cell apoptosis through targeting GSK3B. CONCLUSION: Collectively, the results of this study indicated that miR-132-3p was downregulated in breast cancer tissues and directly targeted GSK3B to be implicated in the modulation of breast cancer cell apoptosis, suggesting that miR-132-3p/GSK3B might be a novel, effective therapeutic target for treating patients with breast cancer.

Plasma p-tau181 Level Predicts Neurodegeneration and Progression to Alzheimer's Dementia: A Longitudinal Study.

Background: Plasma-based biomarkers would be potential biomarkers for early diagnosis of Alzheimer's disease (AD) because they are more available and cost-effective than cerebrospinal fluid (CSF) or neuroimaging. Therefore, we aimed to evaluate whether phosphorylated tau181 (p-tau181) in plasma could be an accurate AD predictor. Methods: Participants from the ADNI database included 185 cognitively unimpaired subjects with negative Aß (CU-), 66 subjects with pre-clinical AD (CU with positive Aß), 164 subjects with mild cognitive impairment with negative Aß (MCI-), 254 subjects with prodromal AD (MCI with positive Aß), and 98 subjects with dementia. Multiple linear regression models, linear mixed-effects models, and local regression were used to explore cross-sectional and longitudinal associations of plasma p-tau181 with cognition, neuroimaging, or CSF biomarkers adjusted for age, sex, education, and APOE genotype. Besides, Kaplan-Meier and adjusted Cox-regression model were performed to predict the risk of progression to dementia. Receiver operating characteristic analyses were performed to evaluate the predictive value of p-tau181. Results: Plasma p-tau181 level was highest in AD dementia, followed by prodromal AD and pre-clinical AD. In pre-clinical AD, plasma p-tau181 was negatively associated with hippocampal volume (ß = -0.031, p-value = 0.017). In prodromal AD, plasma p-tau181 was associated with decreased global cognition, executive function, memory, language, and visuospatial functioning (ß range -0.119 to -0.273, p-value < 0.05) and correlated with hippocampal volume (ß = -0.028, p-value < 0.005) and white matter hyperintensity volume (WMH) volume (ß = 0.02, p-value = 0.01). In AD dementia, increased plasma p-tau181 was associated with worse memory. In the whole group, baseline plasma p-tau181 was significantly associated with longitudinal increases in multiple neuropsychological test z-scores and correlated with AD-related CSF biomarkers and hippocampal volume (p-value < 0.05). Meanwhile, CU or MCI with high plasma p-tau181 carried a higher risk of progression to dementia. The area under the curve (AUC) of the adjusted model (age, sex, education, APOE genotype, and plasma p-tau181) was 0.78; that of additionally included CSF biomarkers was 0.84. Conclusions: Plasma p-tau181 level is related to multiple AD-associated cognitive domains and AD-related CSF biomarkers at the clinical stages of AD. Moreover, plasma p-tau181 level is related to the change rates of cognitive decline and hippocampal atrophy. Thus, this study confirms the utility of plasma p-tau181 as a non-invasive biomarker for early detection and prediction of AD.

MiR-129-5p sensitization of lung cancer cells to etoposide-induced apoptosis by reducing YWHAB.

Background: Lung cancer is the most common cause of death from cancer worldwide and recent studies have revealed that microRNAs play critical roles to regulate lung carcinogenesis. microRNA-129-5p (miR-129-5p) has been reported to regulate cell proliferation and invasion in lung cancer, but its role in lung cancer apoptosis remains unknown. Methods: The expression of miR-129-5p and YWHAB in lung cancer tissues were analyzed from data downloaded from the NCBI Gene Expression Omnibus (GEO) database. Luciferase reporter assay, Western blot and qRT-PCR were used to determine the regulatory effect of miR-129-5p on YWHAB. Cell apoptosis was detected by using the PI/Annexin V Cell Apoptosis Kit. The effect of miR-129-5p and YWHAB on the survival of lung cancer patients was also explored. Results: In this study, by combining the data derived from six GEO database, our results showed that miR-129-5p was downregulated in lung cancer tissues and YWHAB was upregulated in lung cancer patient' serum. A significant negative correlation between miR-129-5p and YWHAB was found in lung cancer tissues. Both the expression of YWHAB and miR-129-5p were associated significantly with prognosis (overall survival) in patients with lung cancer. Overexpression of miR-129-5p promotes VP16-induced lung cancer cell apoptosis and YWHAB was shown to be a direct downstream target of miR-129-5p. Conclusion: Overexpression of expression miR-129-5p contributes to etoposide-induced lung cancer apoptosis by modulating YWHAB.

Low-grade appendiceal mucinous neoplasms confined to the appendix: clinical manifestations and CT findings.

The clinical findings and CT images are investigated in order to fulfill an early preoperative diagnosis and increase awareness of low-grade appendiceal mucinous neoplasm (LAMN) confined to the appendix. 17 cases with histologically proven LAMNs confined to the appendix were included in this study. All patients had received multiphase CT examinations before the surgery. The imaging criteria included shape, size, margin, attenuation, secondary degeneration and internal mass enhancement pattern. In CT images, all cases appeared as oval or tubular cystic masses (average attenuation 20.4±3.6 Hounsfield units), with the longest dimensions ranging from approximately 38 to 106 mm (mean 66.3 mm), and the ratio of length against width was 1.83 in average. The cystic wall was unevenly thickened, with a mean maximal wall thickness of 5.7 mm (>10 mm in 3 cases). The inner capsule wall was rough, and calcification was observed in 3 cases. A few amounts of periappendiceal fat stranding were noted in 2 cases. Mild ring mural enhancement of the cystic wall was seen during the arterial phase, with progressive enhancement during the portal venous phase. In addition, mini enhancing mural nodules was observed in 5 cases. Although preoperative diagnosis of LAMNs confined to the appendix remains challenging, it should be considered when a focal well-defined cystic mass with slightly higher than water attenuation, thickened cystic wall with ring mural enhancement and a characteristic progressive contrast enhancement in CT imaging, especially in older females with non-specific symptoms similar to appendicitis.

Accuracy of Tumor Perfusion Assessment in Rat C6 Gliomas Model with USPIO.

Detailed characterization of the permeability and vascular volume of brain tumor vasculature can provide essential insights into tumor physiology. In this study, we evaluated the consistency of measurements in tumor blood volume and examined the feasibility of using ultrasmall superparamagnetic iron oxide (USPIO) versus gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) as contrast agents for MR perfusion imaging of brain gliomas in C6 Rats. Eighteen rats were intracerebrally implanted with C6 glioma cells, randomly divided into two groups and examined by 3.0T perfusion MR imaging with Gd-DTPA and USPIO. Tumor relative cerebral blood volume (rCBV) and relative maximum signal reduction ratio (rSRRmax) were created based on analysis of MR perfusion images. The mean values for rCBV were 2.09 and 1.57 in the USPIO and the Gd-DTPA groups, respectively, and rSRRmax values were 1.92 and 1.02 in the USPIO and the Gd-DTPA groups, respectively, showing signifi cant differences in both rCBV and rSRRmax between the USPIO and the Gd-DTPA groups (P < 0.05). The results showed that early vascular leakage occurred with gadolinium rather than USPIO in perfusion assessment, revealing that USPIO was useful in perfusion MR imaging for the assessment of tumor vasculature.

Three-dimensional proton magnetic resonance spectroscopy and diffusion-weighted imaging in the differentiation of incidental prostate carcinoma from benign prostate hyperplasia.

The present study evaluated three-dimensional proton magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) features in differentiating incidental prostate carcinoma (IPCa) and benign prostate hyperplasia (BPH) in the central gland of the prostate. The clinical and imaging data of 9 patients with IPCa, 118 patients with BPH [including those with glandular hyperplasia (GH), stromal hyperplasia (SH) and mixed hyperplasia (MH)], were retrospectively analyzed. The mean (choline + creatine)/citrate (CC/C) value of 3D MRS, the apparent diffusion coefficient (ADC) value and the minimal ADC value of DWI were compared between carcinoma and non-carcinoma tissues. The mean CC/C values were 1.04±0.28, and 1.09±0.58 in IPCa and BPH, respectively (t=-0.205, P=0.838). No significant difference in CC/C values (χ2=2.595, P=0.458) could be detected between IPCa, GH, SH and MH groups. The ADC values of the central gland only differed between IPCa (1.48±0.18) ×10-3 and GH (1.60±0.16) ×10-3 mm2/sec (P=0.037). The minimal ADC values were similar between IPCa (1.15±0.10) ×10-3 and BPH (1.14±0.11) ×10-3 mm2/sec, no significant differences could be detected between IPCa and GH (P=0.930), IPCa and SH (P=0.192), and IPCa and MH (P=0.544). Although the ADC values of the central gland of the prostate differed between IPCa and GH, the findings of the present study therefore indicate that combining 3D MRS with DWI cannot potentially improve the detection of IPCa.

Functional role of BTB and CNC Homology 1 gene in pancreatic cancer and its association with survival in patients treated with gemcitabine.

Genetic variation (rs372883C/T) in the 3'-untranslated region of BTB and CNC homology 1 (BACH1) has been associated with pancreatic ductal adenocarcinoma (PDAC) risk in our previous genome-wide association study; however, the action roles of this genetic variation in PDAC remains unknown. Methods:BACH1 expression was measured by quantitative real-time PCR, Western blot and immunohistochemistry. The effects of BACH1 on cell proliferation and sensitivity to gemcitabine were examined by alteration of BACH1 expression in PDAC cells. Angiogenesis was determined in vitro using a human umbilical vein endothelial cell model. Reporter gene assays were conducted to compare the effects of microRNA-1257 on rs372883 variation. The associations between rs372883 variants and survival time in patients treated with gemcitabine were estimated by logistic regression. Results: We found substantially lower BACH1 expression in PDAC compared with normal pancreatic tissues and the rs372883T allele had significantly lower BACH1 levels than the rs372883C allele in both tumor and normal tissues. Knockdown of BACH1 expression provoked proliferation of PDAC cells and angiogenesis, which might result from upregulation of hemeoxygenase-1 that evokes oncogenic AKT and ERK signaling. The rs372883T>C change inhibits interaction of BACH1 with microRNA-1257, resulting in increased BACH1 expression. PDAC patients with the rs372883T allele were more resistant to gemcitabine and had shorter survival time compared with those with the rs372883C allele. Conclusion: These results shed light on the mechanism underlying the associations of BACH1 rs372883 variation with risk of developing PDAC and differential gemcitabine sensitivity in patients.

Prognostic significance of osteopontin in acute myeloid leukemia: A meta-analysis.

Osteopontin (OPN) has been investigated in the field of tumor research for several years. However, the prognostic role of OPN overexpression in acute myeloid leukemia (AML) remains controversial. A meta-analysis of four studies, including a total of 492 patients, was performed to determine the association of OPN with overall survival (OS) in AML patients. The random-effects model of Der Simonian and Laird was used to synthesize data; hazard ratio (HR) with its 95% confidence interval (CI) was used as the effect size estimate. It was observed that serum-based OPN was inversely correlated with OS and the difference was statistically significant (HR=1.83; 95% CI: 1.43-2.35; P<0.001). Experimental findings indicate that OPN overexpression is associated with a poor prognosis in AML and may be of prognostic value for AML stage and metastasis.

Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations.

Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1-E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer.