[Analysis of clinicopathological features of 18 cases of hepatic angiosarcoma].

Objective: To investigate the clinicopathological features, treatment, and prognosis of hepatic angiosarcoma. Methods: Clinicopathological data and prognostic conditions of 18 cases with hepatic angiosarcoma were collected retrospectively. The recurrence-free survival rate and overall survival rate were calculated by the Kaplan-Meier method. A Cox regression analysis was used to explore the survival-related risk factors. Results: There were 12 male and 6 female patients, with an average age of 57 (37 ~ 70) years. The tumor's average diameter was 8.40 (2.00 ~ 18.00) cm. Seven cases had multiple tumors, while two cases had large vessel tumor thrombuses. Microscopically, the tumor tissues were irregularly anastomosed, with vascular lacunar or solid bundle-like weaving, and the tissue morphology mimicked capillary hemangioma, cavernous hemangioma, or angioepithelioma, while tumor cells were spindle-shaped or epithelioid, lined with hobnails in the lumen, or formed papillary structures in the lumen. The proportion of highly, moderately, and poorly differentiated tumors was 4:8:6, with six cases having clear tumor boundaries, eight having microvascular tumor thrombi, and sixteen having blood lake formation. Different levels of expression of CD31, CD34, erythroblast transformation-specific related genes, and Fli-1 markers were demonstrated in all of the cases. Four cases had a P53 mutation, and six cases had Ki-67 > 10%. During the follow-up period of 0.23-114.20 months, the five-year recurrence-free survival rate and overall survival rate were 16.7% and 37.2%, respectively. Cox regression multivariate analysis showed that preoperative symptoms and multiple tumors were significant risk factors for recurrence-free survival, while preoperative symptoms and Ki-67 > 10% were significant risk factors for overall survival. Conclusion: Hepatic angiosarcoma is a rare hepatic mesenchymal tumor with high malignancy and a poor prognosis. Pathological morphology and immunohistochemical marker combinations are needed for a definite diagnosis. However, the complexity of angiosarcomas' histological and cytological conformations and the overlap of pathological features with benign vascular tumors, sarcomas, and carcinomas pose difficulties in the differential diagnosis. Thus, the only effective ways to prolong survival are early detection and radical surgical resection.

[Advances in the diagnostic pathological features of precancerous lesions of hepatocellular carcinoma].

The occurrence of hepatocellular carcinoma (HCC) is a multistep development process through precancerous lesions. A precancerous lesion of HCC is classified into hepatocyte dysplasia at the cytological level and dysplastic nodules at the histological level, and the corresponding lesion subtypes have different risks of canceration. Pathology is the "gold standard" for the diagnosis of early stage HCC and its precancerous lesions. However, it also faces many difficulties and challenges, such as the accumulation of experience in the pathological diagnosis, the understanding and grasp of key points of histopathological diagnosis and differential diagnosis, the combination application of immune and molecular diagnostic markers, and many others. This article briefly discusses the key points of pathological features and differential diagnosis of precancerous lesions of HCC.

Seroprevalence and risk factors of Toxoplasma gondii infection in oral cancer patients in China: a case-control prospective study.

Over the recent years, potential associations between Toxoplasma gondii (T. gondii) infection and cancer risk have attracted a lot of attention. Nevertheless, the association between T. gondii infection and oral cancer remains relatively unexplored. We performed a case-control study of 861 oral cancer patients and 861 control subjects from eastern China with the aim to detect antibodies to T. gondii by enzyme-linked immunosorbent assay (ELISA) in these patients. The results showed that oral cancer patients (21.72%, 187/861) had a significantly higher seroprevalence than control subjects (8.25%, 71/861) (P < 0.001). Among them, 144 (16.72%) oral cancer patients and 71 (8.25%) control subjects were positive for IgG antibodies to T. gondii, while 54 (6.27%) oral cancer patients and 9 (1.05%) controls were positive for IgM antibodies to T. gondii. In addition, multiple logistic analysis showed that T. gondii infection in oral cancer patients was associated with blood transfusion history, keeping cats at home, and oyster consumption. To our knowledge, this is the first study that provided a serological evidence of an association between T. gondii infection and oral cancer patients. However, further studies are necessary to elucidate the role of T. gondii in oral cancer patients.

Common variants on 17q25 and gene-gene interactions conferring risk of schizophrenia in Han Chinese population and regulating gene expressions in human brain.

Recently, two genome-wide association studies (GWASs) of schizophrenia (SCZ) in Han Chinese identified several susceptibility loci. Replication efforts aiming to validate the GWAS findings were made and focused on the top hits. We conducted a more extensive follow-up study in an independent sample of 1471 cases and 1528 matched controls to verify 26 genetic variants by including nine top single-nucleotide polymorphisms (SNPs) that reached genome-wide significance and 17 promising SNPs nominated in the initial discovery phase. rs8073471 in an intron of tubulin-folding cofactor D (TBCD) obtained nominal significance (P<0.01) in single SNP analysis. Logistic regression identified significant interaction between rs3744165 (5'-untranslated region variant of exon 2 of zinc finger protein 750 (ZNF750), and in an intron of TBCD) and rs8073471 (Deviance test P-value=2.77 × 10(-34)). Both SNPs are located at 17q25, an interesting region that has been implicated in SCZ. By using the Genotype-Tissue Expression (GTEx) data set, we implemented an expression quantitative trait loci epistasis analysis to explore the association between the genotype combinations of the two SNPs and gene expression levels in 13 areas of human central nervous system. We observed that rs3744165 × rs8073471 interaction modulated the expression profile of TEAD3 (P=1.87 × 10(-8)), SH3TC2 (P=2.00 × 10(-8)), KCNK9 (P=5.20 × 10(-7)) and PPDPF (P=1.13 × 10(-6)) in postmortem cortex tissue; EFNA1 (P=7.26 × 10(-9)), RNU4ATAC (P=2.32 × 10(-8)) and NUPL2 (P=6.79 × 10(-8)) in cerebellum tissue. To the best of our knowledge, our study is the first one that links TBCD and ZNF750 mutations to SCZ susceptibility and to the transcript levels in human brain tissues. Further efforts are needed to understand the role of those variants in the pathogenesis of SCZ.

Seroepidemiology of Toxoplasma gondii infection in patients with liver disease in eastern China.

The role of the protozoan parasite Toxoplasma gondii in the pathogenesis of liver disease has recently gained much interest. The aim of this study was to determine the prevalence and risk factors associated with T. gondii infection in patients with liver disease from three cities in Shandong and Henan provinces, China. A case-control study was conducted from December 2014 to November 2015 and included 1142 patients with liver disease and 1142 healthy controls. Serum samples were collected from all individuals and were examined with enzyme-linked immunosorbent assay for the presence of anti-T. gondii IgG and IgM antibodies. Information on the demographics, clinical, and lifestyle characteristics of the participants was collected from the medical records and by the use of a questionnaire. The prevalence of anti-T. gondii IgG was 19·7% in patients with liver disease compared with 12·17% in the controls. Only 13 patients had anti-T. gondii IgM antibodies compared with 12 control individuals (1·14% vs. 1·05%, respectively). The highest seroprevalence was detected in patients with liver cancer (22·13%), followed by hepatitis patients (20·86%), liver cirrhosis patients (20·42%), and steatosis patients (20%). Multivariate logistic regression analysis indicated that consumption of raw meat (odds ratio (OR) = 1·32; 95% confidence interval (CI) 1·01-1·71; P = 0·03) and source of drinking water from wells (OR = 1·56; 95% CI 1·08-2·27; P = 0·01) were independent risk factors for T. gondii infection in liver disease patients. These findings indicate that T. gondii infection is more likely to be present in patients with liver disease. Therefore, efforts should be directed toward health education of populations at high risk of T. gondii infection and measures should be taken to protect vulnerable patients with liver disease.

Superiorization-based multi-energy CT image reconstruction.

The recently-developed superiorization approach is efficient and robust for solving various constrained optimization problems. This methodology can be applied to multi-energy CT image reconstruction with the regularization in terms of the prior rank, intensity and sparsity model (PRISM). In this paper, we propose a superiorized version of the simultaneous algebraic reconstruction technique (SART) based on the PRISM model. Then, we compare the proposed superiorized algorithm with the Split-Bregman algorithm in numerical experiments. The results show that both the Superiorized-SART and the Split-Bregman algorithms generate good results with weak noise and reduced artefacts.

[Copy number aberrations of genes related to extrohepatic metastasis-free survival after operation for hepatocellular carcinoma].

Objective: To investigate the molecular markers of copy number aberrations (CNAs) of genes related to extrohepatic metastasis-free survival after the operation for hepatocellular carcinoma (HCC). Methods: The CNA status of 20 candidate genes in 66 HCC samples was detected by microarray comparative genomic hybridization. The associations between gene CNAs and extrohepatic metastasis-free survival were evaluated using the Cox regression model, Log-rank test, and Kaplan-Meier survival analysis. Results: Multivariate Cox analysis revealed that the independent risk factors for metastasis-free survival were MDM4 gain (hazard ratio [HR] = 2.74, 95% confidence interval [CI] = 1.18-6.37, P < 0.05), APC loss (HR = 8.43, 95% CI = 2.48-28.66, P < 0.01), and BCL2L1 gain (HR = 3.45, 95% CI = 1.13-10.52, P < 0.05) and the independent protective factor was FBXW7 loss (HR = 0.32, 95% CI = 0.12-0.89, P < 0.05). By stepwise Cox regression analysis, three CNAs related to metastasis-free survival were screened out: MDM4 gain (HR = 2.71, 95% CI = 1.11-6.64, P < 0.05), APC loss (HR = 7.19, 95% CI = 1.88-27.60, P < 0.005), and FBXW7 loss (HR = 0.16, 95% CI = 0.05-0.46, P < 0.01). There were significant differences in metastasis-free survival rate between the HCC patients with FBXW7 loss and without MDM4 gain or APC loss, those with MDM4 gain and/or APC loss and without FBXW7 loss, and those with other CNA combinations (log-rank test, P < 0.01). Conclusion: MDM4 gain, APC loss, and FBXW7 loss are the independent prognostic factors for extrohepatic metastasis-free survival after the operation for HCC and can be used to predict the risk of extrohepatic metastasis after the operation for HCC.

Loss at 16q22.1 identified as a risk factor for intrahepatic recurrence in hepatocellular carcinoma and screening of differentially expressed genes.

Copy number alteration (CNA) of chromosome 16, a frequent genetic event in tumors including hepatocellular carcinoma (HCC), has been associated with HCC etiology of hepatitis B virus (HBV) and with clinical outcomes in multiple types of cancer. This study identified CNAs in chromosome 16 in relation to intrahepatic recurrence of HCC in a population with high HBV prevalence, and further screened for differentially expressed genes in recurrence-related CNAs. Array comparative genomic hybridization and expression arrays were used to detect CNAs and gene expression differences, respectively. The associations between CNAs and intrahepatic recurrence were analyzed on 66 patients, follow-up period of 3-73 months. One hundred and nine cases were further evaluated regarding the differentially expressed genes. Losses at 16q and 16p were detected in 62.1% and 51.5% of the 66 cases, respectively. The most recurrent CNAs (with frequency >20%) were losses at 16p13.3-13.2, 16p13.11, 16q11.2-22.1, 16q22.1, 16q22.2-24.2 and 16q24.2. Of the CNAs, 16q22.1 loss was significantly associated with unfavorable intrahepatic recurrence-free survival (P = 0.025). Multivariate Cox analysis identified 16q22.1 loss as an independent risk factor for intrahepatic recurrence (HR = 2.32, 95% CI = 1.26-4.27). A panel of 21 genes, including TRADD, PSMB10, THAP11, CTCF and ESRP2, were significantly downregulated in HCCs with 16q22.1 loss compared to those without the loss. These results suggest that loss at 16q22.1 was associated with increased risk for intrahepatic recurrence of HCC, at least in the HBV-prevalence population. Multiple downregulated genes correlated with the loss were screened.

[Molecular mechanism and pathological evaluation strategies for recurrence and metastasis of liver cancer].

The strong invasiveness and metastasis of hepatocellular carcinoma (HCC) are not only the important pathological mechanisms of high recurrence rate and poor long-term outcome, but also the important pathological basis for developing individualized regimens to control metastasis and recurrence in clinical practice. This article introduces the important molecular events in invasion-metastasis cascade discovered in recent years, including the formation mechanism of metastatic niches, methods for molecular pathological evaluation, and standardized pathological diagnosis.

Seroprevalence and associated risk factors of Toxoplasma gondii infection in psychiatric patients: a case-control study in eastern China.

In recent years, the effect of Toxoplasma gondii infection on the cerebrum and neuropsychiatric patients has been increasingly highlighted. However, there is limited information about the epidemiology of T. gondii infection in psychiatric patients in Shandong province, eastern China. Therefore, through a case-control study, 445 patients hospitalized for diacrisis or treatment in Weihai, eastern China, and 445 control subjects from the general population of the same region matched by gender, age, and residence were examined with enzyme-linked immunoassays for the presence of IgG and IgM antibodies to T. gondii and associated sociodemographic and behavioural characteristics in a population of psychiatric patients. Seroprevalence of IgG antibodies to T. gondii in psychiatric patients (77/445, 17·30%) was significantly higher than in control subjects (55/445, 12·36%) (P = 0·038). Fourteen (3·15%) psychiatric patients and 10 (2·25%) control subjects had IgM antibodies to T. gondii (P = 0·408). Multivariate analysis using logic regression showed that T. gondii infection was associated with cats at home and consumption of raw/undercooked meat in psychiatric patients. Considering that most psychiatric patients usually have lower cognitive functioning and additional transmission routes related to their inappropriate behaviours that could enhance the risk of infection, psychiatric patients should be considered as a specific group of T. gondii infection.

Morphology and chronology of diphyodont dentition in miniature pigs, Sus Scrofa.

OBJECTIVE: There is little knowledge about the tooth replacement in large mammals. The aim of this study is to investigate the tooth replacement patterns in Chinese miniature pig (Sus Scrofa). MATERIALS AND METHODS: The developmental patterns of mandibular successional and additional teeth from Chinese miniature pig before and after birth were investigated by microanatomy, immunohistochemistry, and cone beam computed tomography. RESULTS: Secondary dental lamina for successional teeth was not visible until its predecessor progressed to late bell stage. Successional teeth reached early cap stage when their predecessor began to erupt. The development patterns and speed varied between anterior and posterior successional teeth. Additional molars, derived from the free end of additional dental lamina, initiated sequentially in mandible ramus, while previous additional molar progressed into late bell stage. Proliferating cells in the permanent primordium were distributed asymmetrically. CONCLUSIONS: Our findings identify the characteristic patterns about spatiotemporal morphogenesis of successional teeth in context of their predecessor and cascade initiation of additional molars in miniature pigs. Our study provides a basis toward better understanding the mechanisms underlying diphyodont replacement in human and also assists in tooth regeneration and tooth engineering in large animal.

Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine.

The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation, which is introduced into common wheat as a tool of chromosome manipulation for genetic improvement. The Gc chromosome functions similar to a restriction-modification system in bacteria, in which DNA methylation is an important regulator. We treated root tips of wheat carrying Gc chromosomes with the hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were observed in these root tips. The frequency of aberrations differed in wheat containing different Gc chromosomes, suggesting different functions inducing chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome aberration. Gc chromosome 3C induced different degrees of chromosome aberration in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26, demonstrating an inhibition function in common wheat.

X-ray dark-field imaging modeling.

Dark-field images are formed from x-ray small-angle scattering signals. The small-angle scattering signals are particularly sensitive to structural variation and density fluctuation on a length scale of several tens to hundreds of nanometers, offering a unique contrast mechanism to reveal subtle structural features of an object. In this study, based on the principle of energy conservation, we develop a physical model to describe the relationship between x-ray small-angle scattering coefficients of an object and dark-field intensity images. This model can be used to reconstruct volumetric x-ray small-angle scattering images of an object using classical tomographic algorithms. We also establish a relationship between the small-angle scattering intensity and the visibility function measured with x-ray grating imaging. The numerical simulations and phantom experiments have demonstrated the accuracy and practicability of the proposed model.

RAPD and ISSR-assisted identification and development of three new SCAR markers specific for the Thinopyrum elongatum E (Poaceae) genome.

Diploid Thinopyrum elongatum, a wild relative of wheat, contains many agronomically desirable traits and has potential for increasing genetic variability and introducing desirable characters in this crop. Few molecular markers are available for rapid screening of T. elongatum genome segments in the wheat genetic background. We used 36 RAPD primers and 33 ISSR primers to screen for polymorphisms in the common wheat variety Chinese Spring and in T. elongatum. Two RAPD markers and one ISSR marker, designated OPF03(1407), LW10(1487) and UBC841(701), were identified and were specific for the T. elongatum E genome. Three pairs of primers flanking these specific sequences were designed to produce SCAR markers. All three SCAR markers were T. elongatum E genome-specific. Two of these SCAR markers, SCAR(807) and SCAR(577), were present in all seven T. elongatum chromosomes, while SCAR(839) was specific for T. elongatum chromosomes 2E and 3E. These newly developed SCAR markers should be useful for detecting alien genome chromatin or chromosome segments in the genetic background of common wheat.

X-ray scattering tomography for biological applications.

The conventional attenuation contrast imaging does not yield satisfactory sensitivity and specificity for weakly absorbing media, such as biological soft tissues. The x-ray scattering offer an important contrast mechanism to reveal structural features and density fluctuation within an object. This scattering signal carries information at the molecular and supra-molecular level, and has a tremendous implication for biomedical and other applications. In this paper, we develop a scattering imaging approach to reconstruct the electron density distribution of an object and demonstrate its feasibility in the numerical simulation.

Bioluminescence tomography based on the phase approximation model.

A reconstruction method of bioluminescence sources is proposed based on a phase approximation model. Compared with the diffuse approximation, this phase approximation model more correctly predicts bioluminescence photon propagation in biological tissues, so that bioluminescence tomography can accurately locate and quantify the distribution of bioluminescence sources. The compressive sensing (CS) technique is applied to regularize the inverse source reconstruction to enhance numerical stability and efficiency. The numerical simulation and phantom experiments demonstrate the feasibility of the proposed approach.