Fornix alterations induce the disruption of default mode network in patients with adamantinomatous craniopharyngiomas.

Adamantinomatous craniopharyngioma (ACPs) are rare embryonic tumors and often involve the hypothalamus. The underlying neural substrate of the hypothalamic involvement (HI)-related cognitive decline in patients with ACP is still unclear. We aimed to combine the multi-modal neuroimaging and histological characteristics of the ACP to explore the potential neural substrate of the HI-related cognitive decline. 45 patients with primary ACPs (invasive, 23; noninvasive, 22) and 52 healthy control subjects (HCs) were admitted to the cross-sectional study. No significant difference in cognitive domains was observed between HCs and patients with noninvasive ACPs (NACP). Patients with invasive ACPs (IACP) showed significantly lower working memory performance (WM, p = 0.002) than patients with NACP. The WM decline was correlated with the disruption of the medial temporal lobe (MTL) subsystem in the default mode network (DMN) (r = 0.45, p = 0.004). The increased radial diffusivity of the fornix, indicating demyelinating process, was correlated with the disruption of the MTL subsystem (r = -0.48, p = 0.002). Our study demonstrated that the fornix alterations link DMN disruption to HI-related cognitive decline in patients with ACPs. ACPs that invade the hypothalamus can provide a natural disease model to investigate the potential neural substrate of HI-related cognitive decline.

Choroid Plexus Carcinomas With TP53 Germline Mutations: Management and Outcome.

BACKGROUND: Choroid plexus carcinomas (CPCs) are rare pediatric tumors commonly associated with Li-Fraumeni syndrome (LFS), which involves a germline mutation of the tumor suppressor gene TP53. MATERIALS AND METHODS: We retrospectively analyzed the corresponding information of 12 cases, including the effects of surgery and radiotherapy and TP53 germline mutations, to analyse the management strategies. Kaplan-Meier curves and the log-rank test were used to evaluate the progression-free survival (PFS). RESULTS: Twelve CPC patients were included, of which TP53 germline mutations were found in eight cases. All patients underwent surgical resection, and six patients received radiotherapy following with operation after initial diagnosis, one patient received radiotherapy following relapse. It was significantly different (P=0.012 and 0.028) that patients with TP53 germline mutation receiving the gross total resection (GTR) without radiotherapy showed survival advantages. Without TP53 germline mutations also showed survival advantages, but there is no statistical significance (P=0.063). CONCLUSIONS: These findings provide evidence for the therapeutic strategy that radiotherapy should not be considered for patients with TP53 germline mutations.

Derivation of water quality criteria of zinc to protect aquatic life in Taihu Lake and the associated risk assessment.

Zinc is a widely distributed environmental pollutants and has been listed as priority heavy metal pollutant in China. Similar as other heavy metals, toxicity of zinc to aquatic organisms affects by environmental factors such as water hardness. It is necessary to develop regional water quality criteria (WQC) to protect native aquatic life against zinc due to the diversity of aquatic organisms' variability across different water systems, as a concretization and supplement for national zinc WQC. This study derived WQC for zinc by species sensitivity distribution (SSD) curve method. The zinc toxicity data of the aquatic organisms in Taihu Lake used in SSD curve was collected based on published toxicity data for zinc with hardness values and supplemented with acute toxicity tests conducted in this study. Six aquatic organism natives to Taihu Lake were selected to conduct zinc acute toxicity test in a range of hardness conditions. The relationship between water hardness and zinc toxicity was constructed. The criterion maximum concentration (CMC) and criterion continuous concentration (CCC) for zinc in Taihu Lake were then derived, which considered the water quality and taxonomic groups in Taihu Lake. The CMC and CCC were 100.69 µg/L and 30.79 µg/L, respectively. The environmental risk of zinc to Taihu Lake are acceptable, at moderate to low levels. This study has provided a basis for regional water quality criterion derivation and risk assessment in China.

Occurrence and ecological risk assessment of PPCPs in typical inflow rivers of Taihu lake, China.

The occurrence and ecological risks of ten typical pharmaceutical and personal care products (PPCPs) at 12 typical inflow rivers of Taihu lake was investigated in this study. Seven out of the ten typical PPCPs targeted were detected in all the water samples and sediment samples tested. The PPCPs concentration detected were 0-94.91 ng/L for water samples and 0-18.27 ng/g for sediment samples. Sulfamethoxazole (SMZ) and erythromycin (ERY) has relatively higher concentration than other PPCPs in surface water samples, ciprofloxacin (CIP) and ofloxacin (OFX) has relatively higher concentration in the sediment samples. Inflow river-Caoqiao river has a relatively highest contamination of TN and TP, the PPCPs concentration in the river channel, estuary, lake-body also shows high value. This occurs in both the surface water and sediment sample, implied a relatively high pollution input from Caoqiao river. SMZ holds high long-term ecological risks in both surface water and sediment of almost all the tested inflow rivers of Taihu lake. Only ERY has medium short-term risks in surface water, other analyzed PPCPs hold low or insignificant short-terms risks for both surface water and sediments. This study fills the gap of PPCPs ecological risk of surface water and sediment of 12 typical inflow rivers of Taihu Lake, and revealed the importance of control sulfanilamide of the economic belt around Taihu Lake. The results of the present study are useful in providing information for PPCPs control and sustainable water management in freshwater lakes.

Ultrastructural and clinical features of central nervous system melanoma:Analysis of nine cases.

To investigate the ultrastructural and clinical characteristics of melanoma of the central nervous system (CNS). The clinical and electron microscopy pathology data of nine patients with melanoma surveyed from 1993 to 2017 were analyzed. All the CNS melanomas were confirmed by transmission electron microscopy (TEM), including eight cases of primary melanomas and one case of metastatic melanoma. In this study, four stage II melanosomes were intracranial space-occupying, three of which were malignant melanoma, the other one was melanoma. Among the five stage IV melanosomes, four cases were intraspinal space-occupying, the other one was intracranial space-occupying, and the pathological diagnoses were all melanoma. At present, TEM is an important tool for the diagnosis of CNS melanomas. Malignant melanoma has high malignancy and recurrence rate and poor prognosis, while benign melanoma with relatively low recurrence rate, so we speculate that patients with mainly immature melanosomes are more likely to exhibit recurrence.

Effect of microplastic particle size to the nutrients removal in activated sludge system.

Microplastics as emerging environmental pollutants, its effect to the bioprocess of water and wastewater treatment has aroused concern. This study investigated the effects of microplastic polystyrene (PS) particle size to the activated sludge nutrient removal process. The ammonia, nitrite, nitrate and phosphorus removal under various PS particle size during nitrification and denitrification process was tested. The results indicated that with PS particle size 150-300 µm, the ammonia oxidation during nitrification process was inhibited to 71%, 92%, and 80% as compared with the blank reactor, for PS concentration at 0.01 g/L, 0.05 g/L and 0.10 g/L, respectively. The nitrite accumulation during nitrification process was also high at PS particle size 150-300 µm and concentration no less than 0.05 g/L. The nitrate reduction during the denitrification process was all inhibited to 69%-94% as compared with the blank, except for reactor No.4. The phosphate removal during nitrification process was not affected by the existence of microplastics PS, the average removal rate was over 80% after 2 h and over 95% after 3 h, respectively. The microplastics particle size plays important role in affecting the activated sludge nutrient removal process.

Evaluation of microplastic polyvinylchloride and antibiotics tetracycline co-effect on the partial nitrification process.

This study investigated the co-effect of microplastic polyvinylchloride and antibiotics tetracycline to partial nitrification process in treating high ammonia wastewater. The average ammonia oxidation rate of all reactors was 53.58, 56.17 and 42.08 mg·N/L·h in round 1, round 7 and round 13, respectively. The ammonia oxidation rate was reduced to 89.40%, 79.08%, 80.60%, 73.37%, 69.50%, 75.72%, 98.93% and 66.04% from 1st round of test to 13th round of test at reactor R1 to R8. The average nitrosation rate was always over 80% in all conditions tested. Tetracycline removal rate was attributed to sludge adsorption in all reactors and was increased continuously with the increment of tetracycline concentration. The nitrous oxide emission was keep decreasing from round 1 to round 13 in all reactors tested. The microbial community results revealed that with the existence of tetracycline and microplastics, the relative abundance of Bacteroidetes were reduced and Proteobacteria were increased.

Malignant Craniopharyngioma: A Report of Seven Cases and Review of the Literature.

BACKGROUND: Malignant craniopharyngioma is a rare clinical entity; most patients with this disease show transformation from an initially benign craniopharyngioma. The rare prevalence of the disease, nonspecific presenting symptoms, and imaging features that overlap with benign craniopharyngiomas make preoperative identification challenging. METHODS: In this study, we retrospectively evaluated the data of 7 patients diagnosed with malignant craniopharyngioma within a 5-year period in a single center. A thorough review of patient records from Beijing Tiantan Hospital, Capital Medical University, between 2013 and 2018 was performed. After identifying these 7 patients with malignant craniopharyngioma, we evaluated their demographic and clinical characteristics, including symptoms at presentation, imaging characteristics, treatment, and outcomes. RESULTS: Five patients showed transformation from benign craniopharyngiomas, and 2 had de novo malignancy. Two patients were children at diagnosis of malignancy. Patients' average age was 22 years. Headache was the most common presenting symptom, followed by visual field defects and adenohypophyseal dysfunction. Imaging characteristics showed that all patients had giant mass in the sellar, suprasellar, and/or parasellar regions that had invaded surrounding anatomic structures. Of the 5 patients who showed transformation from benign craniopharyngioma, 3 had undergone radiologic treatment before the diagnosis of malignant transformation. CONCLUSIONS: Malignant craniopharyngioma should not be overlooked in patients with a giant sellar mass, especially in young patients who have experienced multiple recurrences of craniopharyngioma and patients who received radiologic therapy.

Evaluation of EZH2 expression, BRAF V600E mutation, and CDKN2A/B deletions in epithelioid glioblastoma and anaplastic pleomorphic xanthoastrocytoma.

INTRODUCTION: Epithelioid glioblastoma (EGBM) and anaplastic pleomorphic xanthoastrocytoma (APXA) are two rare entities with different prognoses. However, they share certain morphological and molecular features. MATERIALS AND METHODS: To better recognize EGBM and APXA and identify the prognostic factors associated with these tumors, EZH2 status, BRAF V600E mutations, and CDKN2A/B deletions were assessed in 15 APXA and 13 EGBM cases. RESULTS: The expression level of EZH2 was found to increase with tumor grade. Overexpression of EZH2 occurred in 69.2% (9/13) of EGBM cases and 20% (3/15) of APXA cases. In addition, 72.7% (8/11) of EGBM and 12.5% (1/8) of APXA cases harbored a CDKN2A homozygous deletion based on fluorescence in situ hybridization. BRAF V600E mutations were detected in 80% (8/10) of EGBM cases and 42.9% (3/7) of APXA cases. Furthermore, EGBM, which exhibited co-existing low-grade glioma-like lesions, was found to have strong EZH2 expression and high Ki-67 indexes only in epithelioid cells and not in low grade lesions. Univariate analysis demonstrated that abundant epithelioid cells, extensive necrosis, EZH2 overexpression and BRAF V600E mutations were significantly associated with decreased overall survival in EGBM and APXA patients (P < 0.05). CONCLUSIONS: The results suggested that testing for EZH2 expression and BRAF V600E mutations might be helpful to evaluate the prognoses of EGBM and APXA patients. The presence of heterogeneous EZH2 expression in biphasic EGBMs could also contribute to malignant progression.

Establishment and quality evaluation of a glioma biobank in Beijing Tiantan Hospital.

BACKGROUND: We established a glioma biobank at Beijing Tiantan Hospital in November, 2010. Specialized residents have been trained to collect, store and manage the biobank in accordance with standard operating procedures. METHODS: One hundred samples were selected to evaluate the quality of glioma samples stored in the liquid nitrogen tank during different periods (from 2011 to 2015) by morphological examination, RNA integrity determination, DNA integrity determination and housekeeping gene expression determination. RESULTS: The majority of samples (95%) had high RNA quality for further analysis with RIN ≥6. Quality of DNA of all samples were stable without significant degradation. CONCLUSION: Storage conditions of our biobank are suitable for long-term (at least five years) sample preservation with high molecular quality.

The clinicopathological features of liponeurocytoma.

To discuss the clinicopathological features of liponeurocytoma, we retrospectively reviewed three liponeurocytoma cases and compared their immunophenotypes and genotypes with those of similar tumors. Furthermore, we reviewed the literature and compared the similarities and differences between cerebellar and intraventricular liponeurocytomas. Two cerebellar and one intraventricular liponeurocytomas were included in the present study. The liponeurocytomas comprised small tumor cells and lipomatous cells. The tumor cells expressed SYN, MAP-2, and NeuN. One case showed atypical histological features. By reviewing the literature, we found that cerebellar liponeurocytoma tended to be more common in females, whereas the converse was true for intraventricular liponeurocytoma. Compared with cerebellar liponeurocytoma, intraventricular liponeurocytoma was more commonly noted in younger adult patients. A high MIB-1 index (>10%) and incomplete tumor resection might represent adverse prognostic factors in patients with liponeurocytoma. We suggest that 'central liponeurocytoma' should be used to include all putative liponeurocytoma sites. The present study identified several morphological, immunohistochemical, and genetic features that may aid in the differential diagnosis of liponeurocytoma. In addition, surgery should be the preferred treatment, and complete tumor resection should be the goal. Additional cases with long-term follow-up are needed to develop optimal management protocols for liponeurocytoma.

A clinicopathologic study of extraventricular neurocytoma.

In 2007, extraventricular neurocytoma was classified as a separate entity among glioneuronal tumors. However, extraventricular neurocytoma is not fully understood and may be misdiagnosed. Here, we describe the clinical and pathological features, prognoses, and treatments of 13 extraventricular neurocytoma cases, and compare their immunophenotypes with those of oligodendroglioma, diffuse astrocytoma, and ependymoma. Six typical and 7 atypical cases comprised the 13 extraventricular neurocytoma cases. Histological features included oligodendroglioma-like perinuclear halo, neuropil-like matrix, ganglion or ganglioid cells, perivascular pseudorosettes, vessel hyalinization, calcifications, and myxoid degeneration. Atypical histological features included increased mitotic figures, focal necrosis, endothelial cell proliferation, and/or a Ki-67 index of >2%. All lesions expressed synaptophysin and microtubule-associated protein-2, which distinguished them from other similar tumors. Two patients with atypical extraventricular neurocytoma had tumor recurrence, one of whom had cerebrospinal fluid dissemination, suggesting that atypical histological features might represent adverse prognostic factors. In conclusion, the present study identified morphological and immunohistochemical features that would aid the differential diagnosis of extraventricular neurocytoma. In addition, radiotherapy with subtotal resection could be considered an effective treatment for extraventricular neurocytoma, but because a pediatric patient died of intracranial hemorrhage during radiotherapy, radiotherapy-related side effects should be considered, especially when treating children. Additional cases with long-term follow-up are needed to develop optimal management protocols for extraventricular neurocytoma.

Targeting of the ß6 gene to suppress degradation of ECM via inactivation of the MAPK pathway in breast adenocarcinoma cells.

Integrin ανß6 has emerged as a potential novel target for anticancer and plays a major role in promoting malignant tumor progression. Recent studies indicate that integrin ανß6 occurs in many cancers. However, whether and how ανß6 is regulated by genetic and epigenetic mechanisms in breast cancer remain unknown. In the present study, two different short hairpin RNAs (shRNAs) targeting the ß6 gene were designed and constructed into pSUPER, respectively, which were transfected into the MCF-7 human breast adenocarcinoma cell line. The ß6-shRNA stably transfected cells were successfully established, and significant lower levels of ανß6 mRNA and protein expression were confirmed. Furthermore, inhibition of integrin ανß6 markedly downregulated the expression of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-3 (MMP-3) and urokinase plasminogen activator (uPA) in tumor conditioned medium. Furthermore, ß6-shRNA-mediated silencing of the ανß6 gene obviously decreased the expression of ERK1/2. In particular, supression of integrin ανß6 caused significant downregulation of the degradation of basement membrane type IV collagen secretion via modulation of the plasminogen activation cascade. Our results thus indicate that ανß6 plays a fundamental role in promoting invasion and growth of breast adenocarcinoma cells. Taken together, this study revealed that targeting of the ß6 gene by RNA interference (RNAi) could efficiently downregulate ανß6 expression and suppress the ERK1/2-dependent extracellular matrix degradation in vitro, which is dependent upon inactivation of the mitogen-activated protein kinase (MAPK) pathway. These findings may offer a useful therapeutic approach to block invasion and migration of breast cancer cells.

Expression and significance of Wnt signaling components and their target genes in breast carcinoma.

The aim of this study was to investigate the expression of ß-catenin, axin, cyclin D1 and c-myc, and their correlation with various clinicopathological factors of breast carcinoma. Using immunohistochemistry, the expression of axin, ß-catenin, cyclin D1 and c-myc proteins was detected in 168 breast carcinomas and 40 normal breast tissue samples, as well as in 72 breast intraductal proliferative lesions. Correlations among the expression of these proteins with the clinicopathological factors of breast carcinomas were subsequently analyzed. Gene mutations of ß-catenin (exon 3) in 44 cases of breast carcinoma were analyzed using polymerase chain reaction (PCR) followed by direct sequencing. In normal tissue, the epithelial cells demonstrated a marked membranous expression of ß-catenin protein at cell-cell boundaries and positive axin expression; cyclin D1 and c-myc expression, however, were negative. The abnormal rate of ß-catenin expression and the overexpression of cyclin D1 and c-myc were higher in breast carcinomas compared with breast cystic hyperplasia tissues. Positive axin expression levels were lower in breast carcinomas compared with breast intraductal proliferative lesions and normal breast tissues. Axin expression correlated inversely with tumor size, histological grade, clinical tumor, node, metastasis (TNM) stage and lymph node metastasis. The abnormal expression of ß-catenin and the overexpression of cyclin D1 were correlated, and the overexpression of c-myc was correlated with tumor size, histological grade, clinical TNM stage and lymph node metastasis. The abnormal expression of ß-catenin was correlated with the overexpression of cyclin D1, but not with the overexpression of c-myc. Lower levels of axin expression were correlated with higher levels of nuclear ß-catenin expression. Mutations in the ß-catenin gene were not detected in 44 cases of breast carcinoma. The abnormal expression of ß-catenin may be key in the carcinogenesis and progression of human breast carcinoma by upregulating the expression of cyclin D1. The abnormal expression of ß-catenin, the reduced expression of axin, and the overexpression of cyclin D1 and c-myc may be useful markers for determining metastasis, providing a prognosis for human breast carcinoma and for guiding treatment.

[Nasal and pharyngeal non-Hodgkin lymphomas and their relationship with Epstein-Barr virus: a report of 158 cases].

OBJECTIVE: To study the clinical features, immunophenotypes and the significance of Epstein-Barr virus infection in primary nasal and pharyngeal non-Hodgkin's lymphomas in Shenyang. METHODS: One hundred and fifty eight cases of primary nasal and pharyngeal non-Hodgkin's lymphomas were included in this study. The samples were stained with haematoxylin and eosin for histological examination. Immunohistochemistry studies were performed using monoclonal antibodies, including CD3 for T-lymphocytes, CD20 for B-lymphocytes, and CD56 and CD57 for NK cells. All cases were reclassified according to the new WHO classification of lymphomas (2001). In situ hybridization detection of EBV-encoded small nuclear RNA (EBER-1) was performed in 99 cases. RESULTS: Overall, 101 (63.9%) of the 158 NHL were extranodal NK/T cell lymphomas (nasal type), 23 (14.6%) were nonspecific peripheral T cell lymphomas and the remaining 34 cases (21.5%) were B cell lymphomas. The primary sites of involvement were the nasal cavity (53.2%, 84/158), the tonsil (24.7%, 39/158) and the pharynx (22.1%, 35/158). Among 99 cases studied by EBER-1 in situ hybridization, a positive detection was seen in 70/71 cases (98.6%) of extranodal NK/T cell lymphoma (nasal type), 8/12 cases (66.7%) of T cell lymphoma, and 7/16 cases (43.8%) of B cell lymphoma. CONCLUSIONS: Among primary nasal and pharyngeal NK lymphomas, extranodal NK/T cell lymphoma (nasal type) is the most common type and is strongly associated with EBV infection. The pathological diagnosis of nasal and pharyngeal lymphomas should take considerations of the anatomic sites and immunophenotypical features.

Analysis of p53, K-ras, c-kit, and beta-catenin gene mutations in sinonasal NK/T cell lymphoma in northeast district of China.

Recently we reported the different frequencies of p53 and c-kit gene mutations among sinonasal NK/T cell lymphoma (NKTCL) in Korea, north China (Beijing), and Japan, suggesting some racial, environmental, or life-style differences as a possible cause of nasal tumorigenesis. In this study, gene mutations in p53, c-kit, K-ras, and beta-catenin gene were analyzed by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) followed by direct sequencing in 20 cases of sinonasal NKTCL from northeast China (Shen Yang). Age of patients ranged from 5 to 63 (median, 40.0) years. p53 gene mutations were found in eight of 20 cases (40%), with exon 4 involvement in 10% of cases. The majority was missense mutations and G:C to A:T transition was predominant. The frequency of the c-kit and K-ras gene mutations was low (5%), while that of the beta-catenin gene was six of 20 cases (30%). From these findings, it is concluded that nasal NKTCL in northeast China shared common features with that in Korea in the younger onset of disease compared to that in Japan and lower frequency of p53 gene mutations with infrequent exon 4 involvement compared to that in Japan and north China. These differences might be caused by migration of susceptible populations or some environmental confounding factors.