[The value of nomogram for predicting microvascular invasion based on clinical and Gd-EOB-DTPA-enhanced magnetic resonance imaging features].

Objective: To investigate the risk factors of microvascular invasion (MVI) in China liver cancer staging system stage Ⅰa (CNLC Ⅰa) hepatocellular carcinoma (HCC), and develop a nomogram for predicting MVI based on clinical and radiographic data. Methods: This retrospective study focused on CNLC Ⅰa HCC patients who underwent radical resection at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2020. Patients' clinical characteristics and laboratory test results and pre-surgery gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging results were collected. The clinical and radiographic risk factors for MVI were identified by univariate and multivariate logistic regression analyses and used for the construction of the predictive nomogram. The nomogram model was then internally validated, and its performance was assessed. Results: A total of 104 patients were divided into the MVI-positive group (n=28) and the MVI-negative group (n=76). Multivariate logistic regression analysis at the P<0.1 level identified serum alpha-ferroprotein >7 ng/ml, total bilirubin >21 µmol/L, prothrombin time >12.5 s, non-smooth margin, and incomplete or absent capsule as risk factors of MVI, based on which a nomogram model was built. The model achieved an area under the curve (AUC) value of 0.867 (95% confidence interval, 0.791-0.944) in the internal validation. The sensitivity and specificity of the nomogram model were 0.786 and 0.829, respectively, with the prediction curve nearly overlapping the ideal curve. Based on the Hosmer-Lemeshow test, the predicted and real results were not significantly different (P=0.956). Conclusions: The probability of MVI of CNLC Ⅰa HCC can be objectively predicted by the monogram model that quantifies the clinical and radiographic risk factors. The model can also help clinicians select individualized surgical plans to improve the long-term prognosis of patients.

[Analysis of risk factors and construction of predictive nomogram for early recurrence after radiofrequency ablation of hepatocellular carcinoma].

Objective: To assess the optimal cut-off value between early recurrence and late recurrence of patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA), and to construct a nomogram to predict early recurrence. Methods: A total of 119 patients with HCC who recurred after RFA in Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2017 were identified. The optimal cut-off value to distinguish early and late recurrence was determined based on differences in post recurrence survival (PRS) by minimum P-value approach. The clinical and radiographic risk factors for early recurrence were identified by univariate and multivariate Logistic regression analysis. The predictive nomogram was constructed by these factors and internally validated. Results: The optimal cut-off value to distinguish early recurrence and late recurrence was 12 months after RFA (P=0.005). The patients were divided into early recurrence group (47 cases) and late recurrence group (72 cases). The lower quartile PRS (Q1-PRS) and lower quartile overall survival (Q1-OS) were 11.1 and 19.1 months in the early recurrence group, which were shorter than 31.6 and 81.0 months in the late recurrence group (P=0.005 and P<0.001, respectively). The independent risk factors of early recurrence were alpha fetoprotein (AFP) (OR=8.459, 95%CI: 2.231-32.073), albumin(ALB) (OR=0.251, 95%CI: 0.047-1.339), number of lesions (OR=3.842, 95%CI: 1.424-10.365) and peritumoral enhancement (OR=8.05, 95%CI: 1.23-52.80), which were further incorporated into constructing the predictive nomogram of early recurrence of HCC after RFA. Internal validation results showed the area under the curve, sensitivity, specificity of the receiver operating characteristic (ROC) curve were 0.839, 68.1% and 93.1%, respectively. The calibration curve showed the predicted curve of nomogram was close to the ideal curve. Hosmer-Lemeshow test showed there was no significant difference between the predicted results of nomogram and the actual results (P=0.424). Conclusions: An interval of 12 months after RFA is the optimal cut-off value for defining early recurrence and late recurrence. The nomogram is integrated by clinical and radiographic features, which can potentially predict early recurrence of HCC after RFA and may offer useful guidance for individual treatment or follow up.

Histone modifications of Notch1 promoter affect lung CD4+ T cell differentiation in asthmatic rats.

Asthma is an inflammatory disease of the airways, and the current treatment in managing asthma is the control of inflammation. Notch signaling pathway has been linked to T-cell imbalance. The present study aimed to explore the histone modifications of Notch1 promoter in normal and asthmatic lung CD4+ T cells. Chromatin immunoprecipitation analysis showed that the acetylation levels of total H3, H4, site-specific H3K9, H3K14, H3K27, H3K18, H4K16, and the trimethylation levels of H3K4, H3K79 of Notch1 gene promoter were increased significantly in asthmatic lung CD4+ T cells compared to the control group, which correlated with increased P300, PCAF activity and decreased HDAC1, HDAC2 activity. After intervention of garcinol, a potent inhibitor of histone acetyltransferases, in asthmatic lung CD4+ T cells, HAT activity decreased significantly and the increased Notch1 and hes-1 expression was reversed. The total H3ac, H4ac, site-specific H3K9ac, H3K14ac, H3K27ac, H3K18ac, H4K16ac and H3K79me3 levels of Notch1 gene promoter decreased significantly, and the H3K4me3, H3K9me3, H4K20me3 levels had no significant difference. We further investigated the suppressive effects of GAR on asthmatic parameters. Results showed that the levels of IL-4, IL-5 and IL-13 were significantly reduced and a small reverse trend was found in the level of IFN-g after GAR treatment. Furthermore, the expression of NF-κB and AP-1 reduced significantly. These results suggest that asthma is associated with changes in the epigenetic status of Notch1 promoter, including abnormal histone acetylation and methylation, and GAR may have applications in the treatment of asthma.

YES-associated protein 1 promotes adenocarcinoma growth and metastasis through activation of the receptor tyrosine kinase Axl.

Yes-associated protein 1 (YAP1), a nuclear effector of the Hippo pathway, plays an important role in tumorigenesis and progression of multiple cancers. The present study aimed to investigate the clinical significance of YAP1 and receptor tyrosine kinase Axl expression in human lung adenocarcinomas (LAC). We further explored possible molecular mechanisms mediated by YAP1 in LAC and gastric adenocarcinoma (GAC) cells. Forty-nine cases of human LAC and normal lung tissue (NLT) were collected. The expression of YAP1 and Axl was assessed by immunohistochemical assay through tissue microarray procedure and the clinicopathologic characteristics of all patients were analyzed. Using a loss of function approach, we investigated the effects of small hairpin RNA (shRNA)-mediated knockdown of YAP1 on the expression of Axl, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-9 (MMP-9), and the proliferative activities and invasive potential in LAC A549 and GAC SGC-7901 cell lines. As a result, the expression of YAP1 and Axl was found in LAC tissues with higher strong reactivity rate compared to the NLT (87.8 percent vs.60.8 percent, P=0.000; 77.6 percent vs 0.0 percent, P=0.000), but they did not associate with the age, gender, tumor size, TNM staging or lymph node metastases of LAC patients (each P>0.05). Spearman rank correlation analysis showed a positive correlation between YAP1 and Axl expression. Furthermore, knockdown of YAP in vitro markedly down-regulated the expression of Axl, PCNA and MMP-9, and inhibited the proliferation and invasion of LAC and GAC cells. Taken together, YAP1 and Axl are highly expressed in LAC compared to the NLT, and knockdown of YAP1 may inhibit the proliferation and invasion of adenocarcinoma cells through downregulation of the Axl pathway, representing a potential therapeutic target for the treatment of cancer.

A research for the relationship between human papillomavirus and human uterine cervical carcinoma. II. Molecular genetic and ultrastructural study on the transforming activity of recombinant retrovirus containing human papillomavirus type 16 subgenomic sequences.

In order to elucidate the role of HPV-16 in the development of genital cancer, NIH3T3 cells were transfected by HPV-16 whole genome and its two early genes, E6-E7. Besides ordinary calcium phosphate/DNA coprecipitation technique, a newly designed recombinant retrovirus containing the HPV-16 genome or subgenomes was used to infect cells for transfer of the target genes. The transforming activities have been demonstrated to be most efficient when a bioengineering technique of this kind is used. HPV-16 DNA was proved to have transforming potential for NIH3T3 cells, and the DNA of HPV-16 was proved to undergo multisite integration into transformed cells and nude mice tumour cells. The E6-E7 open reading frames are sufficient for transforming NIH3T3 cells independently in vitro, which implies that E6-E7 open reading frames are transforming genes or even viral oncogenes of HPV-16. The RNA transcribed by the E6-E7 of HPV-16 was expressed in transformed cells and in tumour cells of nude mice. The use of a recombinant retrovirus for gene transfer in this study is much more efficient than that of calcium phosphate/DNA coprecipitation. The lack of a tissue-culture system suitable for HPV replication in vitro makes HPV gene recombination into a specially engineered retrovirus for viral-mediated gene transfer of particular significance for the possible application of viral carcinogenesis, both in vitro and in vivo, for basic and clinical research.

Viral etiology of cervical carcinoma. Human papilloma virus and herpes simplex virus type 2.

The possible role of human papilloma virus (HPV) and herpes simplex virus type 2 (HSV-2) in the viral etiology of cervical carcinoma was investigated a series of cervical lesions were studied for the presence of HPV and HSV-2 DNA sequences as well as HPV and HSV-2 antigens by DNA dot blot hybridization technique and high-specificity PAP staining method. The results obtained were correlated with the histologic diagnosis. HPV 16 DNA sequences detected in cervical carcinoma biopsies were 43%, whereas HSV-2 DNA sequences were only 8%. HPV antigens detected in cervical dysplasia were 31%, whereas those detected in cervical carcinoma and cervicitis were the least. HSV-2 antigens were detected in chronic cervicitis, dysplasia and cervical carcinoma. The difference in positive rate between the cervical carcinoma and cervicitis groups was statistically significant, (chi-square test, P less than 0.01). No HPV DNA and HSV-2 DNA sequences were found in the same specimen, although both HPV DNA sequences and HSV-2 antigens were found in the same sample in some cases. The results indicate that the viral etiology of cervical carcinoma may be multifactorial. Both HSV-2 and HPV may be associated with cervical carcinoma, but the mechanisms involved are different. HSV-2 and HPV may act synergistically in the development of cervical carcinoma.

[Studies on the physical state of human papillomavirus 16 DNA in biopsies of patients with cervical carcinoma].

Five biopsies from cervical cancer containing human papillomavirus (HPV) 16 DNA sequences confirmed by dot blot analysis were used to study the physical state of HPV 16 DNA in cervical cancer. Southern blots prepared after: 1) sample DNA was cleaved with restriction enzymes which do not digest HPV 16;2) sample DNA was cleaved with restriction enzymes (pstI) capable of digesting HPV 16 DNA; 3) sample DNA was not digested with restriction enzymes; and 4) two-dimensional agarose gel electrophoresis was performed on sample DNA digested with enzymes which do not cleave HPV 16 DNA. It was shown that HPV 16 DNA was integrated into the cellular genome.

A novel, multidisciplinary clinic for complex visual problems in older people.

BACKGROUND: Visual symptoms in older people can be complex and inadequately explained by eye pathology alone. Psychological and neurodegenerative processes may manifest as complex visual symptoms, and thus some patients may be poorly served by a purely ophthalmic approach. We have developed a novel multidisciplinary clinic with input from neurology, ophthalmology, and psychiatric specialists. Here, we describe the patient population, disease prevalence, and potential impact of this new clinic. METHODS: A retrospective audit of paper and electronic records from June 2010 to February 2012 and selected case reports. RESULTS: Between June 2010 and February 2012 48 patients attended the clinic. Notes were available for 47 (98%). Mean age was 76.2 (range 48-92). The main presenting complaints were hallucinations, followed by nonspecific visual deficit, double vision, blurred vision, and visuospatial deficit. Cognitive impairment was noted in 68% (32/47) of patients, of which 16/32 (50%) were new diagnoses. We were able to give a diagnosis to 98% (46/47) of patients; of these, 74% (35/46) were new diagnoses. A total of 6% (3/47) were felt to have presentations attributable to eye pathology alone, whereas 89% (42/47) were felt to have a neuropsychiatric component. Management included referral to other clinics for continuing care in 43% (20/47) and initiation of therapy in 36% (17/47). The three case reports demonstrate cases, where our multidisciplinary approach aided diagnosis and management of patients with complex visual symptoms. CONCLUSION: A combined clinic with neurological, ophthalmic, and psychiatric input is an effective way to diagnose and manage complex visual problems in older people.