Intratumoural and peritumoural CT-based radiomics for diagnosing lepidic-predominant adenocarcinoma in patients with pure ground-glass nodules: a machine learning approach.

AIM: To develop and validate a diagnostic model utilising machine-learning algorithms that differentiates lepidic predominant adenocarcinoma (LPA) from other pathological subtypes in patients with pure ground-glass nodules (pGGNs). MATERIALS AND METHODS: This bicentric study was conducted across two medical centres and included 151 patients diagnosed with lung adenocarcinoma based on histopathological confirmation of pGGNs. The training cohort consisted of 99 patients from Institution 1, while the test cohort included 52 patients from Institution 2. Radiomics features were extracted from both tumours and the 2 mm peritumoural parenchyma. The tumoural and peritumoural radiomics were designated as Modeltumoural and Modelperitumoural, respectively. The diagnostic efficacy of various models was evaluated through the receiver operating characteristic (ROC) curve analysis. Subsequently, a machine-learning-based prediction model that combined Modeltumoural, Modelperitumoural, and Modelclinical-radiological was developed to differentiate LPA from other pathological subtypes in patients with pGGNs. RESULTS: Modeltumoural achieved area under the curve (AUC) values of 0.762 and 0.783 in the training and validation sets, respectively. Modelperitumoural attained AUCs of 0.742 and 0.667, and Modelclinical-radiological generated an AUC of 0.727 and 0.739 in the training and validation sets, respectively. Among the machine-learning models evaluated, gradient boosting machines demonstrated the best diagnostic efficacy, with accuracy, AUC, F1 score, and log loss values of 0.885, 0.956, 0.943, and 0.260, respectively. CONCLUSION: The combined model based on machine learning that incorporated tumour and peritumoural parenchyma, as well as clinical and imaging characteristics, may offer benefits in assessing the pathological subtype of pGGNs.

Famine Exposure during Early Life and Risk of Cancer in Adulthood: A Systematic Review and Meta-Analysis.

OBJECTIVES: Emerging evidences have explored the association between famine exposure during early life and cancer risk in adulthood, but the results remain controversial and inconsistent. This study aimed to provide a comprehensive evidence on the relation of famine exposure to later cancer risk. DESIGN: Systematic review and meta-analysis. METHODS: Relevant reports published up to March, 2022 were identified by searching PubMed, Embase, Web of sciences and Medline databases. Pooled relative ratios (RRs) with 95% confidence intervals (CIs) were used to evaluate the effect famine exposure on cancer risk. RESULTS: Totally, 18 published articles with 6,061,147 subjects were included in this study. Compared with unexposed group, early life famine exposure dramatically increased the risk of cancer in adulthood (RR=1.13, 95% CI: 1.04-1.22). The pooled RRs were different in terms of sex, exposure severity, exposure period, famine type, study design type and cancer location. A remarkably elevated risk for cancer was discerned in women exposed to famine (RR=1.09, 95% CI: 1.00-1.18), severe exposure (RR=1.12, 95% CI: 1.02-1.22) and adolescence exposure (RR=1.76, 95% CI: 1.02-2.50), Chinese famine exposure (RR=1.55, 95% CI: 1.29-1.82) and cohort studies (RR=1.28, 95% CI: 1.13-1.42). Moreover, a significant association of early-life famine exposure with increased risk of breast (RR=1.16, 95% CI: 1.05-1.27) and stomach cancers (RR=1.89, 95% CI: 1.24-2.54) was observed. CONCLUSION: This meta-analysis suggests that exposure to famine during early life may increase the risk of cancer in adulthood. The above-mentioned association is pronounced in women exposed to famine, severe exposure, adolescence exposure, Chinese famine, cohort studies, breast and stomach cancers. It is essential for decision-makers to take targeted measures for improving population awareness regarding the long-term effect of early life nutritional status.

Development of a novel combined nomogram integrating deep-learning-assisted CT texture and clinical-radiological features to predict the invasiveness of clinical stage IA part-solid lung adenocarcinoma: a multicentre study.

AIM: To develop a novel combined nomogram based on deep-learning-assisted computed tomography (CT) texture (DL-TA) and clinical-radiological features for the preoperative prediction of invasiveness in patients with clinical stage IA lung adenocarcinoma manifesting as part-solid nodules (PSNs). MATERIALS AND METHODS: This study was conducted from January 2015 to October 2021 at three centres: 355 patients with 355 PSN lung adenocarcinomas who underwent surgical resection were included and classified into the training (n=222) and validation (n=133) cohorts. PSN segmentation on CT images was performed automatically with a commercial deep-learning algorithm, and CT texture features were extracted. The least absolute shrinkage and selection operator was used for feature selection and transformed into a DL-TA score. The combined nomogram that incorporated the DL-TA score and identified clinical-radiological features was developed for the prediction of pathological invasiveness of the PSNs and validated in terms of discrimination and calibration. RESULTS: The present study generated a combined nomogram for predicting the invasiveness of PSNs that included age, consolidation-to-tumour ratio, smoking status, and DL-TA score, with a C-index of 0.851 (95% confidence interval: 0.826-0.877) for the training cohort and 0.854 (95% confidence interval: 0.817-0.891) for the validation cohort, indicating good discrimination. Furthermore, the model had a Brier score of 0.153 for the training cohort and 0.135 for the validation cohort, indicating good calibration. CONCLUSION: The developed combined nomogram consisting of the DL-TA score and clinical-radiological features and has the potential to predict the individual risk for the invasiveness of stage IA PSN lung adenocarcinomas.

Sodium MRI at 7T for Early Response Evaluation of Intracranial Tumors following Stereotactic Radiotherapy Using the CyberKnife.

BACKGROUND AND PURPOSE: Conventionally, early treatment response to stereotactic radiotherapy in intracranial tumors is often determined by structural MR imaging. Tissue sodium concentration is altered by cellular integrity and energy status in cells. In this study, we aimed to investigate the feasibility of sodium MR imaging at 7T for the preliminary evaluation of radiotherapeutic efficacy for intracranial tumors. MATERIALS AND METHODS: Data were collected from 16 patients (12 men and 4 women, 24-75 years of age) with 22 intracranial tumors who were treated with stereotactic radiation therapy using CyberKnife at our institution between December 1, 2016, and August 15, 2019. Sodium MR imaging was performed at 7T before and 48 hours, 1 week, and 1 month after CyberKnife radiation therapy. Tissue sodium concentration (TSC) was calculated and analyzed based on manually labeled regions of tumors. RESULTS: Ultra-high-field sodium MR imaging clearly showed the intratumoral signal, which is significantly higher than that of normal tissue (t = 5.250, P <.001)., but the edema zone has some influence. The average TSC ratios of tumor to CSF in the 22 tumors, contralateral normal tissues, edema zones, frontal cortex, and frontal white matter were 0.66 (range, 0.23-1.5), 0.30 (range, 0.15-0.43), 0.58 (range, 0.25-1.21), 0.25 (range, 0.17-0.42), and 0.30 (range, 0.19-0.49), respectively. A total of 12 tumors in 8 patients were scanned at 48 hours, 1 week, and 1 month after treatment. The average TSC at 48 hours after treatment was 0.06 higher than that before treatment and began to decrease at 1 week. The TSC ratios of 10 continued to decline and 2 tumors increased at 1 month, respectively. Tumor volume decreased by 2.4%-99% after 3 months. CONCLUSIONS: Changes in the TSC can be quantified by sodium MR imaging at 7T and used to detect radiobiologic alterations in intracranial tumors at early time points after CyberKnife radiation therapy.

CT texture analysis-based nomogram for the preoperative prediction of visceral pleural invasion in cT1N0M0 lung adenocarcinoma: an external validation cohort study.

AIM: To develop a nomogram based on computed tomography (CT) texture analysis for the preoperative prediction of visceral pleural invasion in patients with cT1N0M0 lung adenocarcinoma. MATERIALS AND METHODS: A dataset of chest CT containing lung nodules was collected from two institutions, and all surgically resected nodules were classified pathologically based on the presence of visceral pleural invasion. Each nodule on the CT image was segmented automatically by artificial-intelligence software and its CT texture features were extracted. The dataset was divided into training and external validation cohorts according to the institution, and a nomogram for predicting visceral pleural invasion was developed and validated. RESULTS: Of a total of 313 patients enrolled from two independent institutions, 63 were diagnosed with visceral pleural invasion. Three-dimensional (3D) CT long diameter, skewness, and sphericity, and chronic obstructive pulmonary disease were identified as independent predictors for visceral pleural invasion by multivariable logistic regression. The nomogram based on multivariable logistic regression showed great discriminative ability, as indicated by a C-index of 0.890 (95% confidence interval [CI]: 0.867-0.914) and 0.864 (95% CI: 0.817-0.911) for the training and external validation cohorts, respectively. Additionally, calibration of the nomogram revealed good predictive ability, as indicated by the Brier score (0.108 and 0.100 for the training and external validation cohorts, respectively). CONCLUSIONS: A nomogram was developed that could compute the probability of visceral pleural invasion in patients with cT1N0M0 lung adenocarcinoma with good calibration and discrimination. The nomogram has potential as a reliable tool for clinical evaluation and decision-making.

[Effect of rebamipide on the acute gouty arthritis in rats induced by monosodium urate crystals].

OBJECTIVE: To investigate the role of rebamipide in the treatment of acute gout arthritis rats induced by monosodium urate (MSU) crystal. METHODS: Forty-two male rats were randomly divided into three groups (n=14). Group A was treated with oral rebamipide, group B with oral colchicine, and group C with oral placebo. The rats were monitored for the induction of arthritis with clinical manifestations and pathological changes, and the levels of interleukin (IL)-1ß、IL-6、IL-10, and tumor necrosis factor (TNF)-α in serum were measured. RESULTS: In group C, the clinical score and swelling index reached the maximum in 24 h, and then gradually decreased to 72 h. After 24 h of model induced, the clinical scores in group C were significantly higher than those in group A and group B [2 (1-3) vs. 0 (0-1) vs. 1 (0-2), P < 0.01], the swelling indexes in group C were significantly higher than those in group A and group B [0.36 (0.16-0.52) vs. 0.11 (0-0.20) vs. 0.12 (0-0.16), P < 0.01]. Histologically, after 24 h of model induced, there was a large number of neutrophil infiltration in the synovium of group C [scale score: 4 (2-4)], and there was no significant inflammatory cell infiltration in group A [1 (0-2)] and group B [1 (0-2)], the difference was statistically significant (P < 0.001). After 24 h of model induced, the levels of IL-1ß, IL-6, IL-10, and TNF-α in serum of group C were significantly higher than those in group A and B [IL-1ß: (41.86±5.72) vs. (27.35±7.47) vs. (27.76±5.28) ng/L, IL-6: (1 575.55±167.11) vs. (963.53±90.22) vs. (964.08±99.31) ng/L, IL-10: (37.96±3.76) vs. (21.68±4.83) vs. (16.20±2.49) ng/L, TNF-α: (21.32±1.34) vs. (15.82±2.54) vs. (17.35±7.47) µg/L, P < 0.001]. CONCLUSION: Rebamipide has a protective effect on acute gout arthritis rats induced by MUS crystals.

17 beta-estradiol affects proliferation and apoptosis of canine bone marrow mesenchymal stem cells in vitro.

Emerging researches in humans, pigs and mice, highlighted that estrogen plays a pivotal role in self-renewal and differentiation of bone marrow mesenchymal stem cells (BMSCs). The present study aimed at evaluating effects of 17 beta-estradiol (E2) on proliferation and apop-tosis of canine-derived bone marrow mesenchymal stem cells (cBMSCs) in vitro. The results showed that E2 supplementation at the concentration of 10-11 M promoted the proliferation of cBMSCs by CCK-8 assay and RT-qPCR analysis for the proliferation-related genes, with proliferating cell nuclear antigen (PCNA), cyclin-D1 (CCND1) being up-regulated and cyclin--dependent kinase inhibitor 1B (CDKN1B) being down-regulated. Contrarily, analysis of fluores-cence-activated cell sorting (FACS) and RT-qPCR demonstrated that E2 supplementation above 10-11 M had inhibitory effects on the proliferation of cBMSCs and induced apoptosis. Intriguingly,cBMSCs still possessed the capability to differentiate into osteoblasts and adipocytes with 10-11 M E2 addition. Taken together, this study determined the optimal culture condition of cBMSCs in vitro, and has important implications for further understanding the regulatory effect of E2 on the self-renewal of cBMSCs, which are helpful for the clinical application of BMSCs.

[Effect of non-diabetic postoperative hyperglycemia on complications after pancreaticoduodenectomy].

Objective: To examine the association of hyperglycemia and postoperative complications in non-diabetic patients underwent pancreaticoduodenectomy(PD). Methods: The clinical data of 209 non-diabetic patients who underwent PD from January 2012 to June 2018 at Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University and met the inclusion criteria were retrospectively analyzed. According to the diagnostic criteria of postoperative hyperglycemia, the patients were divided into postoperative hyperglycemia group (167 cases, 79.9%) and control group(42 cases, 20.1%). The propensity score matching(PSM) method was used to eliminate the difference between groups(caliper value=0.02; 38 cases in control group including 30 males and 8 females with age of 59.0 years;38 cases in postoperative hyperglycemia group including 32 males and 6 females with age of 61.0 years;37 cases of pancreatic head carcinoma,30 cases of periampullary carcinoma and 9 cases of benign diseases). A comparative analysis was applied for preoperative data, surgical related indicators and postoperative complication rates.The receiver operating characteristic(ROC) curve was used to calculate the area under the curve(AUC) of blood glucose values on postoperative day 1,3 and 5(POD1, POD3, POD5), to determine the high-risk blood glucose cutoff value of complications and to evaluate its sensitivity and specificity for the prediction of postoperative complications. Results: Univariate analysis showed that the differences in gender, body mass index, preoperative blood glucose, and serum urea nitrogen levels were statistically significant before PSM.There was no significant difference in the preoperative data between the two groups after PSM. Compared with the control group, the incidence of postoperative pancreatic fistula (31.6% vs. 5.3%), abdominal infection(29.0% vs. 7.9%) and Clavien-Dindo Ⅲ-Ⅴ complications(31.6% vs.7.9%) were statistically different(χ(2)=7.092,P=0.008; χ(2)=4.290,P=0.038; χ(2)=5.316,P=0.021), respectively. According to the AUC on POD3,the blood glucose value ≥8.860 mmol/L was an independent risk factor for pancreatic fistula with sensitivity of 58.3% and specificity of 76.9%,the blood glucose value ≥9.130 mmol/L was an independent risk factor for abdominal infection with sensitivity of 54.5% and specificity of 81.5% and the blood glucose value ≥7.685 mmol/L was independent risk factor of Clavien-Dindo Ⅲ-Ⅴ complications with sensitivity of 75.0% and specificity of 57.7%. Conclusions: Postoperative hyperglycemia in non-diabetic patients is associated with postoperative pancreatic fistula, abdominal infection, and Clavien-Dindo Ⅲ-Ⅴ complications.According to the early postoperative blood glucose value,the occurrence of postoperative pancreatic fistula, abdominal infection and Clavien-Dindo Ⅲ- Ⅴ complications can be effectively predicted.

[Clinical study of FibroTouch and six serological models for assessing the degree of liver fibrosis in patients with chronic hepatitis B].

Objective: To evaluate the using value of FibroTouch and six serological models in detecting the degree of liver fibrosis in patients with chronic hepatitis B, in an attempt to provide reference for accurate diagnosis. Methods: Two hundred and fifty-eight cases with chronic hepatitis B admitted to Xixi Hospital of Hangzhou from September 1, 2015 to September 1, 2017 were selected. All patients underwent liver histopathological examination and FibroTouch measurement to determine liver stiffness (LSM). Serum biochemical parameters were detected and the scoring values of six serological models were calculated. SAS 9.4 statistical software was used for statistical analysis, and the correlation between FibroTouch and the six serological models was analyzed by Spearman correlation. The diagnostic value of FibroTouch and six serological models was analyzed by receiver operating characteristic curve (ROC) based on liver histopathological findings. Results: The median LSM of 258 cases with chronic hepatitis B was 9.4 (6.5-13.8) kPa. In the six serological models, the median value of aspartate transaminase to platelet ratio index (APRI), FIB-4 index, S-index, Forn's index, PRPindex, and FIB-5 were 0.42 (0.28-0.62), 1.27 (0.78-2.03), 0.11 (0.07-0.20), 6.95 (5.89-8.51), 0.000 8 (0.000 6-0.000 9),and 38.59 (36.28-40.97). FibroTouch had positive correlation with APRI, FIB-4, S-index, Forn's index, PRP, fibrosis stage (r= 0.73,P< 0.001) and inflammation grade, and had negative correlation with FIB-5, and both had statistical significance. The area under curve (AUC) of FT-LSM at S≥2, S≥3, S = 4 were 0.89, 0.90 and 0.85, respectively, which was significantly higher than serological models (P< 0.001). The AUC of S-index model at S≥2, S≥3, S = 4 were higher than other five serological models. Conclusion: The diagnostic performance of FibroTouch is significantly better than serological model. S-index model has the best diagnostic performance in the six serological models, and the combination of S-index and FT-LSM may better diagnose the grading of liver fibrosis, and thus can be applied and promoted in clinic.

[Clinical application of the Chinese version of Cornell assessment of pediatric delirium: a pilot study].

Objective: To evaluate the clinical application of Chinese version of Cornell assessment of pediatric delirium (CAPD) scale in children by a pilot study. Methods: A prospective observational study. From June 2017 to December 2017, the original CAPD screen was translated into Chinese and debugged cross-culturally according to the guidelines, which was further applied in the Department of Critical Care Medicine, Children's Hospital of Chongqing Medical University. The clinical data of 250 patients who were evaluated with the Chinese version of CAPD scale and Richmond agitation-sedation scale were extracted and analyzed with chi-square test or Mann-Whitney U test. Cronbach's α coefficient,Split-half coefficient and intra-group correlation coefficient were used to evaluate the reliability, while exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to evaluate the structural validity of the scale. The result was compared with the gold standard diagnostic results to evaluate the diagnostic efficacy of the CAPD. Results: Sixty-one (24.4%) patients had delirium during pediatric intensive care unit hospitalization,and significant differences existed between them and 189 patients without delirium in age (χ(2)=11.220, P=0.011), rates of mechanical ventilation (χ(2)=6.691, P=0.010) and length of PICU hospitalization (Z=10.656, P=0.001). The Chinese version of the CAPD scale had high discrimination among the 8 items in the main table without skewed distribution and discrete items. The internal and external reliability of the scale were preferable as the Cronbach's α coefficient was 0.819 and ICC value was 0.835. The KMO value of EFA was 0.834 and Bartlett spherical test showed statistical significance (χ(2)=661.440, P<0.01). CFA constructed a two-factor structural equation model with favorable fit index:Chi-square/degree of freedom (DF) ratio was 1.786 (χ(2)=33.930, P=0.019), goodness of fit index (GFI) was 0.967,adjusted GFI was 0.938,root mean square of the approximate error (RMSEA) was 0.056. A good diagnostic efficacy of this scale was demonstrated by receiver operating characteristic curve analysis as when the cut-off was 10, the area under curve was 0.99 (95%CI: 0.97-0.99), sensitivity was 96.7% (95%CI: 88.7-99.6), specificity was 93.1% (95%CI: 88.5-96.3), positive likelihood ratio was 14.0 (95%CI: 13.2-14.9), and the negative likelihood ratio was 0.035 (95%CI: 0.008-0.200). Conclusion: The Chinese version of the CAPD Scale has favorable reliability,validity,diagnostic efficacy, as well as feasibility, which should be applied in evaluation of pediatric delirium in clinical observation and research in the future.

Improvac induces immunocastration by affecting testosterone levels and disrupting spermatogenesis in male broiler chickens.

Immunocastration (vaccination against Gonadotropin-releasing hormone (GnRH)) has been regarded as a friendly substitution to physical castration in animals. To date, a few studies have reported the use of Improvac for immunocastration in boar and one study in broiler chickens; however, there is an apparent dearth of scientific evidence regarding the application of Improvac for immunocastration in birds. In the present study, we evaluated the effects of Improvac-based immunocastration on testosterone levels and spermatogenesis in broiler chickens and the effects of Improvac on the expression of genes related to testosterone biosynthesis and metabolism as well as spermatogenesis. The birds were randomly divided into 4 groups (n = 30 each): Control group (non-immunized), Early group (immunized with Improvac at week 3), Late group (immunized with Improvac at week 6), and Early + Late group (immunized with Improvac at weeks 3 and 6). Immunization with Improvac significantly improved the average daily gain compared to the Control group. Of note, following Improvac vaccination, the reproductive efficiency was significantly decreased in male broiler chickens. Furthermore, parameters such as the serum testosterone concentration, spermatogenesis, and the expression levels of genes related to testosterone metabolism (Cyp17A1, Cyp19, HSD3B1, and HSD17B3) and spermatogenesis (Cyclin A1 and Cyclin A2) were significantly reduced in the immunized groups compared to the Control group. Taken together, these findings reveal that immunization against GnRH can be achieved, at least partially, in male broiler chickens. The results of our study also support the hypothesis of using Improvac as an alternative solution to caponization, with considerably improved animal welfare.

[Establishment of multiple predictor models of severe acute pancreatitis in elderly patients].

Objective: To investigate the prognostic factors related to the severity of acute pancreatitis and to establish the multiple predictor models of severe acute pancreatitis(SAP) in elderly patients. Methods: Clinical data of 146 consecutive elderly patients who met the inclusion criteria between January 2014 and May 2017 at Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University were retrospectively collected and analyzed, wherein 88 cases were mild acute pancreatitis, 29 cases were moderately severe acute pancreatitis and 29 cases were SAP. The patients data were subjected to univariate analysis and multiple classified Logistic regression analysis for independent prognostic factors of the severity of acute pancreatitis in elderly patients. Unweighted predictive score(unwScore) and weighted predictive score(wScore)for SAP in elderly patients were established according which the receiver-operating characteristic(ROC) curves of independent prognostic factors and predictor models were produced. The cutoff values of independeut prognostic factors and predictor models were determined. The area under the curve, the sensitivity, the specificity, the positive predictive value and the negative predictive value to verify the predictive efficiency of the independent prognostic factors and predictor models were calculated. Results: Procalcitonin(PCT)(Z=10.564, P=0.000), blood urea nitrogen(BUN)(Z=22.231, P=0.003), serum creatinine(Scr)(Z=14.151, P=0.030), serum calcium(Z=34.979, P=0.032) and pleural effusion(χ(2)=28.463, P=0.015) were independent prognostic factors of the severity of acute pancreatitis by univariate analysis and multiple classified Logistic regression analysis in elderly patients. Respectively, the area under the curve of PCT, BUN, Scr, serum calcium and pleural effusion were 0.908, 0.737, 0.701, 0.753, 0.712, the sensitivity were 0.828, 0.621, 0.552, 0.690, 0.517, the specificity were 0.915, 0.786, 0.846, 0.966, 0.906, the positive predictive value were 70.6%, 41.9%, 47.1%, 83.3%, 57.7%, the negative predictive value were 95.5%, 89.3%, 88.4%, 92.6%, 88.3%. Respectively, the area under the curve of unwScore and wScore were 0.915 and 0.953, the sensitivity were 0.759 and 0.931, the specificity were 0.889 and 0.915, the positive predictive value were 62.9% and 73.0%, the negative predictive value were 93.7% and 98.2%. Conclusions: PCT, BUN, Scr, serum calcium and pleural effusion were independent prognostic factors of the severity of acute pancreatitis in elderly patients. The multiple predictor models of SAP in elderly patients have a good predictive efficiency, which may provide valuable clinical reference for prediction and treatment.

The comparison of thoracoscopic-laparoscopic esophagectomy and open esophagectomy: A meta-analysis.

OBJECTIVE: The objective of this study was to perform a meta-analysis to evaluate the effects of thoracoscopic-laparoscopic esophagectomy (TLE) and open esophagectomy (OE) in the treatment of esophageal cancer. METHODS: A literature search was performed using PubMed, Embase, and Google Scholar databases for relevant keywords and the medical subject headings. After we had screened further, 13 clinical trials were included in the final meta-analysis. Specific odds ratios (ORs), standardized mean differences (SMDs), mean differences (MDs), and confidence intervals (CIs) were calculated. RESULTS: The outcomes of treatment effects included anastomotic leakage, blood loss, number of lymph nodes harvested, and operating time. Comparing OE for esophageal cancer patients, the pooled OR of anastomotic leakage was 0.89 (95% CI = [0.47, 1.68]), the pooled SMD of blood loss was - 0.56 (95% CI = [-0.77, -0.35]), the pooled MD of lymph nodes harvested was - 0.93 (95% CI = [-2.35, 0.50]), and the pooled SMD of operating time was 0.31 (95% CI = [0.02, 0.59]). CONCLUSION: TLE was found to significantly decrease patients' blood loss. There is no difference of anastomotic leakage and the number of lymph nodes harvested between TLE and OE.

Cytogenetic landscape and impact in blast phase of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy.

The landscape of additional chromosomal alterations (ACAs) and their impact in chronic myeloid leukemia, blast phase (CML-BP) treated with tyrosine kinase inhibitors (TKIs) have not been well studied. Here, we investigated a cohort of 354 CML-BP patients treated with TKIs. We identified +8, an extra Philadelphia chromosome (Ph), 3q26.2 rearrangement, -7 and isochromosome 17q (i(17q)) as the major-route changes with a frequency of over 10%. In addition, +21 and +19 had a frequency of over 5%. These ACAs demonstrated lineage specificity: +8, 3q26.2 rearrangement, i(17q) and +19 were significantly more common in myeloid BP, and -7 more common in lymphoid BP; +Ph and +21 were equally distributed between two groups. Pearson correlation analysis revealed clustering of common ACAs into two groups: 3q26.2 rearrangement, -7 and i(17q) formed one group, and other ACAs formed another group. The grouping correlated with risk stratification of ACAs in CML, chronic phase. Despite the overall negative prognostic impact of ACAs, stratification of ACAs into major vs minor-route changes provided no prognostic relevance in CML-BP. The emergence of 3q26.2 rearrangement as a major-route change in the TKI era correlated with a high frequency of ABL1 mutations, supporting a role for TKI resistance in the changing cytogenetic landscape in CML-BP.

Bioinformatic analysis of RNA-seq data unveiled critical genes in rectal adenocarcinoma.

OBJECTIVE: RNA-seq data of rectal adenocarcinoma (READ) were analyzed with bioinformatics tools to unveil potential biomarkers in the disease. MATERIALS AND METHODS: RNA-seq data of READ were downloaded from The Cancer Genome Atlas (TCGA) database. Differential analysis was performed with package edgeR. False discovery rate (FDR) < 0.05 and |log2 (fold change)|>1 were set as cut-off values to screen out differentially expressed genes (DEGs). Gene coexpression network was constructed with package Ebcoexpress. Gene Ontology enrichment analysis was performed for the DEGs in the gene coexpression network with DAVID online tool. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was also performed for the genes with KOBASS 2.0. RESULTS: A total of 620 DEGs, 389 up-regulated genes, and 231 down-regulated genes, were identified from 163 READ samples and 9 normal controls. A gene coexpression network consisting of 71 DEGs and 253 edges were constructed. Genes were associated with ribosome and focal adhesion functions. Three modules were identified, in which genes were involved in muscle contraction, negative regulation of glial cell proliferation and extracellular matrix organization functions, respectively. Several critical hub genes were disclosed, such as RPS2, MMP1, MMP11 and FAM83H. Thirteen relevant small molecule drugs were identified, such as scriptaid and spaglumic acid. A total of 8 TFs and 5 miRNAs were acquired, such as MYC, NFY, STAT5A, miR-29, miR-200 and miR-19. CONCLUSIONS: Several critical genes and relevant drugs, TFs and miRNAs were revealed in READ. These findings could advance the understanding about the disease and benefit therapy development.

P120ctn may participate in epithelial-mesenchymal transition in OSCC.

AIM: Oral squamous cell carcinoma (OSCC) is the eighth most common cause of cancer death. OSCC cells can easily invade tissues and metastasize to the cervical lymph nodes. Understanding the molecular basis of OSCC metastasis would facilitate the development of new therapeutic approaches to the disease. MATERIALS AND METHODS: To identify the potential role of catenin (P120ctn) in the progression of OSCC, HN4 cells (derived from a primary OSCC) and HN12 cells (derived from a lymph node metastasis in the same patient) were used in the present study. The samples of 28 patients with OSCC were examined to determine the expression of P120ctn and E-cadherin (E-cad; E: Epithelial) in vivo. Then, P120ctn was subsequently knocked down in HN4 cells (HN4/shP120ctn) and overexpressed in HN12 cells (HN12/P120ctn). Invasion and migration capacity, as well as the expression of the epithelial-to-mesenchymal transition (EMT) markers N-cadherin and vimentin were detected. RESULTS: The results showed a positive correlation between the expression of P120ctn and E-cad in OSCC samples. The overexpression of P120ctn led to a decrease in both invasion and migration capacity of HN12 cells accompanied by a decrease in EMT markers. In contrast, knockdown of P120ctn led to an increase in both invasion and migration capacity accompanied by an increase in EMT markers. CONCLUSION: Considered together, we concluded that P120ctn might regulate EMT in OSCC through E-cad. The proper expression of P120ctn might therefore serve as a therapeutic goal for the inhibition of OSCC progression.

Nifuroxazide induces apoptosis and impairs pulmonary metastasis in breast cancer model.

Breast carcinoma is the most common female cancer with considerable metastatic potential. Signal transducers and activators of the transcription 3 (Stat3) signaling pathway is constitutively activated in many cancers including breast cancer and has been validated as a novel potential anticancer target. Here, we reported our finding with nifuroxazide, an antidiarrheal agent identified as a potent inhibitor of Stat3. The potency of nifuroxazide on breast cancer was assessed in vitro and in vivo. In this investigation, we found that nifuroxazide decreased the viability of three breast cancer cell lines and induced apoptosis of cancer cells in a dose-dependent manner. In addition, western blot analysis demonstrated that the occurrence of its apoptosis was associated with activation of cleaved caspases-3 and Bax, downregulation of Bcl-2. Moreover, nifuroxazide markedly blocked cancer cell migration and invasion, and the reduction of phosphorylated-Stat3(Tyr705), matrix metalloproteinase (MMP) MMP-2 and MMP-9 expression were also observed. Furthermore, in our animal experiments, intraperitoneal administration of 50 mg/kg/day nifuroxazide suppressed 4T1 tumor growth and blocked formation of pulmonary metastases without detectable toxicity. Meanwhile, histological and immunohistochemical analyses revealed a decrease in Ki-67-positive cells, MMP-9-positive cells and an increase in cleaved caspase-3-positive cells upon nifuroxazide. Notably, nifuroxazide reduced the number of myeloid-derived suppressor cell in the lung. Our data indicated that nifuroxazide may potentially be a therapeutic agent for growth and metastasis of breast cancer.

Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing.

BACKGROUND: To determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalin-fixed, paraffin-embedded (FFPE) tumors obtained through routine clinical practice, selected cancer-related genes were evaluated and compared with alterations seen in frozen tumors obtained through research studies. PATIENTS AND METHODS: DNA samples obtained from 252 FFPE HNSCC were analyzed using next-generation sequencing-based (NGS) clinical assay to determine sequence and copy number variations in 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. Human papillomavirus (HPV) status was determined by presence of the HPV DNA sequence in all samples and corroborated with high-risk HPV in situ hybridization (ISH) and p16 immunohistochemical (IHC) staining in a subset of tumors. Sequencing data from 399 frozen tumors in The Cancer Genome Atlas and University of Chicago public datasets were analyzed for comparison. RESULTS: Among 252 FFPE HNSCC, 84 (33%) were HPV positive and 168 (67%) were HPV negative by sequencing. A subset of 40 tumors with HPV ISH and p16 IHC results showed complete concordance with NGS-derived HPV status. The most common genes with genomic alterations were PIK3CA and PTEN in HPV-positive tumors and TP53 and CDKN2A/B in HPV-negative tumors. In the pathway analysis, the PI3K pathway in HPV-positive tumors and DNA repair-p53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPV-positive nasal cavity/paranasal sinus carcinoma shared similar mutational profiles. CONCLUSION: The genomic profile of FFPE HNSCC tumors obtained through routine clinical practice is comparable with frozen tumors studied in research setting, demonstrating the feasibility of comprehensive genomic profiling in a clinical setting. However, the clinical significance of these genomic alterations requires further investigation through application of these genomic profiles as integral biomarkers in clinical trials.