[Studies on lithium in the environment and its effects on the central nervous system].

This paper introduces the distribution of global lithium resources and absorption, distribution, metabolism and excretion of lithium in the human body, discussing the positive effect of lithium in the environment on the nervous system and its neuroprotective mechanism. The tiny amounts of lithium that enter the body through the food chain have been linked to beneficial health effects, such as improved cognition and reduced depression and violence. However, the safe dose range of lithium is narrow, and the health effects of drinking high concentrations of lithium water in high-lithium areas are unclear. It is necessary to study the health effects and mechanisms of different doses of lithium, especially high concentrations of lithium in the environment.

[Advances on the research of the environmental risk factors of children autism].

Autism spectrum disorder is a lifelong neurodevelopmental disorder, characterized by social interaction and communication impairments, accompanied by repetitive behaviors. Little is known about the causes and contributing factors for autism. It is difficult to prevent and cure, and has become a globe public health problem. With the development in the prevalence of autism, the idea how the environmental factors cause the autism, gains all attentions. Summarizing latest epidemiological studies and experimental evidence, this review is focused on the effect of environmental factors, including air pollutant, heavy metal and pesticides, and discussed the relation between environmental risk factors and autism. The results showed that risks of autism in children may increase following in prenatal exposure to air pollutants, heavy metal and pesticides. It is needed to do the research on the mechanism of environmental risk factor and autism for more prevention, treatment and control suggestions.

Species history and divergence times of viviparous and oviparous Chinese toad-headed sand lizards (Phrynocephalus) on the Qinghai-Tibetan Plateau.

The Qinghai-Tibetan Plateau (QTP) is an important biogeographical area and has recently become a focus for biodiversity studies. Phyrnocephalus lizards form a widespread Eurasian group with oviparous and viviparous reproductive modes, but two previous mtDNA studies of species from around the QTP have provided different phylogenetic hypotheses. We analysed three loci (mtDNA, RAG-1, AME) from all recognised Chinese Phrynocephalus species to reconstruct the speciation history of the group and to estimate species divergence times. The effects of mtDNA partitioning strategy on phylogenetic inference were examined. Bayes factor comparisons of marginal likelihoods (mLs) estimated using stepping-stone sampling revealed that partitioning strategy had a major impact on mL. Nevertheless, it had a negligible effect on the inferred tree topology. The impact of hard-bound uniform or equivalent soft-bound gamma speciation time calibration priors as well as the use of a fixed topology (as opposed to integration over all possible species histories) on divergence time estimation were also assessed, and found to have little impact on posterior estimates. All three gene trees and the species tree supported the hypothesis that the Chinese species form oviparous and viviparous sister clades. This was in agreement with an early mtDNA study but differed from a subsequent reanalysis of the mtDNA data. Inclusion of mtDNA from more widely distributed Phrynocephalus (from previous studies) indicates that the oviparous P. interscapularis from Central Asia lies outside the clade of Chinese viviparous and oviparous species, but that other Asian oviparous species lie within the Chinese oviparous clade. The median of the posterior on the divergence time of Chinese oviparous and viviparous species was 9.7 Ma ago (95% interval: 7.2-13.0 Ma ago), which coincides with major uplifting of the QTP and indicates that viviparity evolved when this clade became restricted to regions of high elevation. We also found that cladogenesis within the viviparous clade began around 5 Ma ago whereas those in the oviparous clade began around 8.6 Ma ago. We establish more robust estimates of divergence times and relationships within this important group and so provide improved insights into the origins of Phrynocephalus diversity across the QTP.

Outpatient screening with the Royal Free Hospital-Nutrition Prioritizing Tool for patients with cirrhosis at risk of malnutrition.

OBJECTIVES: Malnutrition is common among inpatients with cirrhosis. However, data on the prevalence of malnutrition among stable ambulatory patients with cirrhosis is lacking. We sought to investigate the prevalence of patents at risk of malnutrition (ARMN) among ambulatory patients with cirrhosis using the Royal Free Hospital-Nutrition Prioritizing Tool (RFH-NPT) and the Malnutrition Universal Screening Tool (MUST) and compare their correlation to clinical outcomes. METHODS: Patients attending an outpatient liver cirrhosis clinic at a tertiary hospital were screened for ARMN using both the RFH-NPT and MUST (defined by a score of ≥2 for either tool). Differences in clinical outcomes after 6 mo were compared. RESULTS: There were 134 patients recruited. The RFH-NPT identified more ARMN patients compared with MUST (32.8% versus 8.2%; P < 0.01; Cohen κ, 0.27 [95% CI, 0.12-0.42]; P < 0.001). Fluid overload at recruitment was the only independent predictor of disagreement between the RFH-NPT and MUST (odds ratio [OR], 43.14; 95% CI, 8.70-214.00; P < 0.001). There was a trend toward an increased risk of mortality for ARMN patients by the RFH-NPT (hazard ratio, 3.58; 95% CI, 0.81-15.83; P = 0.06) but not by the MUST (P = 0.62). The incidence of hospital admissions in ARMN patients was higher by the RFH-NPT, with an incidence rate ratio of 13.27 (95% CI, 5.11-43.70; P < 0.001), but not in ARMN patients by the MUST (P = 0.85). Being ARMN by the RFH-NPT was the only independent predictor of hospital admissions (OR, 15.08; 95% CI, 2.47-91.98; P = 0.003). CONCLUSIONS: The RFH-NPT identified more ARMN patients when compared with the MUST, especially among patients with fluid overload. Patients at risk of malnutrition were at an increased risk of hospital admissions and possibly death.

DGCR8 promotes the metastasis in triple-negative breast cancer by epigenetically regulating TGF-ß.

OBJECTIVE: Breast cancer (BC) is one of the most ordinary fatal cancers. Recent studies have identified the vital role of genes in the development and progression of Tri-negative breast cancer (TNBC). In this research, DGCR8 was studied to identify how it functioned in the metastasis of TNBC. PATIENTS AND METHODS: DGCR8 expression of tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in 50 TNBC patients. Wound healing assay and transwell assay were used to observe the changes in the biological behaviors of TNBC cells through knockdown or overexpression of DGCR8. In addition, qRT-PCR and Western blot assay were performed to discover the potential target protein of DGCR8 in TNBC. RESULTS: DGCR8 expression level in TNBC samples was higher than that of adjacent ones. Besides, the migration ability and invasion ability of TNBC cells were inhibited after DGCR8 was silenced, while they were promoted after DGCR8 was overexpressed. In addition, TGF-ß was downregulated after silencing of DGCR8 in TNBC cells, while TGF-ß was upregulated after overexpression of DGCR8 in TNBC cells. Furthermore, TGF-ß was upregulated in TNBC tissues, which was positively associated with DGCR8. CONCLUSIONS: Our study uncovers a new oncogene in TNBC and suggests that DGCR8 can enhance TNBC cell migration and invasion via targeting TGF-ß, which provides a novel therapeutic target for TNBC patients.

Immunohistochemical expression of GCIP in breast carcinoma: relationship with tumour grade, disease-free survival, mucinous differentiation and response to chemotherapy.

AIMS: Grap2 and cyclin-D interacting protein (GCIP) is a putative tumour suppressor in human cancer. The aim was to investigate its prognostic significance in human breast carcinoma. METHODS AND RESULTS: Immunohistochemical analysis of breast carcinoma specimens from 107 female patients was performed. Decreased cytoplasmic expression of GCIP was detected in breast carcinomas compared with normal ductal epithelium (P < 0.001). Higher GCIP scores were observed in patients with lower histological grade, mucinous carcinomas and better clinical outcome (P < 0.05). Disease-free survival was significantly longer in patients with high GCIP scores than in those with low GCIP scores (P = 0.010). However, GCIP expression was independent of the status of oestrogen receptor, progesterone receptor, Her-2/neu and cancer stage. Moreover, in patients receiving neoadjuvant chemotherapy, those with higher GCIP scores showed potentially more reduction of tumour size compared with those with lower GCIP scores (borderline significance, P = 0.053). CONCLUSIONS: The current data provide evidence that decreased expression of GCIP in vivo is present in human breast carcinoma and indicate that GCIP is a potential indicator of good prognosis. In patients receiving neoadjuvant chemotherapy, it may also have predictive value for the chemotherapeutic response.

Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing α-tubulin acetylation in breast cancer.

Increasing evidence indicates that long non-coding RNAs (lncRNAs) act as important regulatory factors in tumor progression. However, their roles in breast cancer remain largely unknown. In present studies, we identified aberrantly expressed long intergenic non-coding RNA APOC1P1-3 (lincRNA-APOC1P1-3) in breast cancer by microarray, verified it by quantitative real-time PCR, and assessed methylation status in the promoter region by pyrosequencing. We also investigated the biological functions with plasmid transfection and siRNA silencing experiments, and further explored their mechanisms by RNA pull-down and RNA immunoprecipitation to identify binding proteins. We found that 224 lncRNAs were upregulated in breast cancer, whereas 324 were downregulated. The lincRNA-APOC1P1-3 was overexpressed in breast cancer, which was related to tumor size and hypomethylation in its promoter region. We also found that APOC1P1-3 could directly bind to tubulin to decrease α-tubulin acetylation, to inactivate caspase-3, and to inhibit apoptosis. This study demonstrates that overexpression of APOC1P1-3 can inhibit breast cancer apoptosis.

Induction of antitumor immunity with combination of HER2/neu DNA vaccine and interleukin 2 gene-modified tumor vaccine.

The therapeutic effects of both cytokine-secreting tumor vaccine and DNA vaccine were studied using mouse MBT-2 bladder cancer cells as a model. Cytokine-secreting MBT-2 cells were obtained by infecting cells with retroviral particles containing interleukin (IL) 2-, IL-4-, or granulocyte-macrophage colony-stimulating factor (GM-CSF)-expression vector. The MBT-2-IL-2 cells were not tumorigenic in syngenic C3H mice at all. Tumor formation decreased significantly for the MBT-2-GM-CSF cells. MBT-2-IL-2, -IL-4, and -GM-CSF cells were killed by irradiation and tested as tumor vaccines. The irradiated MBT2-IL-2 cells could complete protect mice from the growth of the preexisting tumor cells, and the immune memory lasted for 8 months. On the other hand, irradiated MBT-2-IL-4 and MBT-2-GM-CSF cells were less effective. When the loading tumor mass increased, all tumor vaccines lost protective effects. DNA vaccine encoding the tumor antigen neu was additionally tested to improve the therapeutic efficacy. Coinjection of 60 microg pSV-neu DNA was effective in enhancing the antitumor effects of MBT2-IL-2; however, DNA vaccine alone cannot prevent the progression of the preexisting tumor. Immunohistochemical analysis of tumor infiltrate revealed massive increase of CD4+ lymphoid cells in the group of mice treated with both DNA vaccine and IL-2-secreted tumor vaccine. Western blotting demonstrated the presence of anti-neu antibody in the serum from immunized mice. In contrast, combination of DNA vaccine and MBT-2-GM-CSF has no additive effect. The results indicate the combination of DNA vaccine and IL-2-secreting tumor vaccine can additionally improve therapeutic efficacy, and the efficacy is correlated with the increase of CD4+ T lymphocytes and anti-neu antibody.

Synthesis, characterization, and biodistribution of [113mIn]TE-BAT: a new myocardial imaging agent.

In order to develop a new myocardial perfusion agent, new lipid-soluble complexes containing a net charge of +1 were evaluated. Synthesis, radiolabeling, characterization, and biodistribution of a unique indium complex, [113mIn]TE-BAT (tetraethyl-bis-aminoethanethiol), are described. The complex formation between In +3 and TE-BAT ligand is rapid, simple, and of high yield (greater than or equal to 95%). This process is amenable to kit formulation. The complex has a net charge of +1 and an In/ligand ratio of 1:1. Biodistribution in mice shows higher heart uptake and longer retention as compared to 201TI. This complex, when labeled with 111In, shows promise as a possible tracer for myocardial perfusion imaging.

Detection of bcl-2 and p53 in thymoma: expression of bcl-2 as a reliable marker of tumor aggressiveness.

The distinction between noninvasive and invasive or malignant thymoma has been severely compromised by a lack of objective morphological criteria. A reliable marker of tumor aggressiveness is, therefore, mandatory for predicting the tumor behavior. Forty thymic epithelial tumors, including 5 noninvasive thymomas, 18 invasive thymomas, and 17 thymic carcinomas (Rosai's classification) were investigated for expression of bcl-2 and p53 proteins by immunohistochemistry. The thymic epithelial cells showed positive immunostain for bcl-2 in 0, 7, and 16 of these categories, respectively. Thymic carcinomas had a significantly higher proportion of bcl-2 expression than thymomas (P < .0001). A significantly higher expression of bcl-2 protein was also shown in thymoma-associated myasthenia gravis (P < .05). However, p53 showed no correlation with the histological subtypes nor clinical aggressiveness. Bcl-2 expression appeared to be positively correlated with p53 immunoreactivity, but this result was not statistically significant (P = .07). In conclusion, these data indicate that bcl-2 expression correlates with aggressiveness in thymic epithelial neoplasms.

Detection of Kaposi's sarcoma-associated herpesvirus-like DNA sequence in vascular lesions. A reliable diagnostic marker for Kaposi's sarcoma.

A new herpesvirus-like DNA sequence (KSHV) has been recently identified in Kaposi's sarcoma (KS) from patients with AIDS and non-AIDS patients. To verify the specificity of the association of this new viral DNA with KS, a total of 155 cases of benign and malignant vascular neoplasms sharing similar histogenesis of endothelial derivation were analyzed for the presence of this KSHV sequence using the published 330-233 primers by polymerase chain reaction (PCR). The results revealed that all 17 cases of KS, both AIDS and non-AIDS, were positive for this KSHV, whereas the remaining 138 cases of vascular lesions other than KS, including 15 cases of angiosarcoma, showed negative reaction. These results confirm and extend the previous observation that this KSHV sequence is specifically associated with KS and is a reliable diagnostic marker to distinguish KS, particularly at its early stage, from other vascular lesions.

Comparison of the MB/BacT and BACTEC MGIT 960 system for recovery of mycobacteria from clinical specimens.

A total of 543 specimens were cultured in parallel with the MB/BacT and BACTEC MGIT 960 systems and on the conventional solid media. Mycobacteria were identified from 95 (17.5%) specimens, including 63 (66.3%) Mycobacterium tuberculosis and 32 (33.7%) nontuberculous mycobacteria. The recovery rates for the MB/BacT, MGIT 960, and solid media were 91.6, 87.4, and 54.7%, respectively, for all mycobacteria; the recovery rates were 93.6, 88.9, and 63.4%, respectively, for M. tuberculosis complex alone, and 87.5, 84.4, and 37.5%, respectively, for all nontuberculous mycobacteria. The mean times to detection of all mycobacteria by individual systems were 13. 9, 8.7, 31.7 days for the MB/BacT, MGIT 960 and solid media, respectively, 13.9, 9.3, 32.9 days for M. tuberculosis alone, and 14. 1, 8.1, 27.2 days for all nontuberculous mycobacteria. The contamination rates of the MB/BacT and MGIT 960 were 10.2 and 5.4%, respectively. With regard to detection times and recovery rates, both automated systems are superior to the conventional media (all p < 0.005). As compared to the MB/BacT, the MGIT 960 detected mycobacterial growth more rapidly (p < 0.001), and had a lower contamination rate (p = 0.003); however, there was no statistically significant difference in recovery rates between these two systems. These results indicate that both MGIT 960 and MB/BacT systems are rapid, sensitive, and efficient methods for the recovery of mycobacteria from clinical specimens.

Synthesis of PCR-derived, digoxigenin-labeled DNA probes for in situ detection of Epstein-Barr early RNAs in Epstein-Barr virus-infected cells.

A PCR-derived digoxigenin-labeled DNA probe was used for for Epstein-Barr early RNA (EBER) in situ hybridization in formalin-fixed paraffin-embedded tissues. The results showed that the hybridization signal was morphologically distinct and the intensity of signal was comparable with those by RNA riboprobe. The advantages of using PCR-derived DNA probes for EBER in situ hybridization include: (1) the synthesis of digoxigenin-labeled DNA probes is easy and simple by PCR; (2) the labeled amplification product can be used as a probe without further purification; (3) DNA probes are potentially more stable than RNA probes; and (4) the preparation of DNA probes is relatively efficient and rapid. It is concluded that this technique is an ideal candidate for detection of EBER expression in clinical specimens.

Pancreas divisum with early pancreatic cancer--presenting as chronic obstructive pancreatitis.

A 61-year-old man experienced four bouts of pancreatitis in 1 year. Detailed history taking and a series of examinations, including sonography, computed tomography scan, and endoscopic retrograde cholangiopancreatography (ERCP), revealed pancreas divisum on the first admission. He was treated conservatively. However, repeated ERCP on the fourth admission, 1 year later, showed a small filling defect in the tail of the pancreatic duct. A distal pancreatectomy was carried out. Pathological studies revealed a small papillary adenocarcinoma (1.5 x 1.0 x 0.5 cm) confined to the pancreatic duct grossly with minimal parenchymal invasion microscopically. He has been free from cancer and pancreatitis for 13 months since the operation.

Papillary cystic tumor of the pancreas: a case indistinguishable from oncocytic carcinoma.

A case of papillary cystic tumor (PCT) of the pancreas in a 55-year-old woman is described. She presented with a gradually enlarging and painless abdominal mass for > 26 years. The tumor was encapsulated and measured 16 x 12 x 10 cm. The gross features and conventional light microscopic appearance of this tumor were consistent with the previously reported cases of PCT. Perineural and capsular invasions were found. In addition to the densely packed blue granules in the cytoplasm demonstrated by phosphotungstic acid-hematoxylin stain, ultrastructural study revealed the tumor cells to be packed with numerous mitochondria. These oncocytes comprised almost all the non-necrotic tumor areas. Therefore, this case was indistinguishable pathologically from oncocytic carcinoma of the pancreas. DNA flow cytometry showed a diploid pattern and low S phase fraction, indicating that the tumor has a low proliferative activity and a favorable prognosis.

Hypervolemic hemodilution may protect the rat's striatal neurons from ischemic injury by reducing the extracellular dopamine.

In vivo voltammetry (IVV) was used in rats with transient brain ischemia to measure changes in extracellular concentrations of dopamine (DA) and its metabolites in the corpus striatum. Striatal neuronal damage were also rated on a scale of 0-3 (0 = no damage; 3 = maximum cell loss). The striatal extracellular levels of DA and its metabolites increased by 12-fold during the 30 min of brain ischemia and returned to control values at 30 min after reperfusion. In another group treated with 4-5 ml of 10% human albumin intravenously infused 30 min before brain ischemia, both augmented striatal DA (and its metabolites) levels and striatal neuronal damages were reduced as compared to the ischemic control group (P < 0.05, unpaired Student's t-test). These results suggest that hypervolemic hemodilution protects the striatal neurons from ischemic injury by reducing the extracellular striatal DA release in rats.

Interleukin-1 receptor antagonist attenuates the heat stroke-induced neuronal damage by reducing the cerebral ischemia in rats.

The effects of interleukin-1 receptor antagonist (IL-Ira) on both local cerebral blood flow and neuronal damage of the hypothalamus, corpus striatum, cortex or thalamus were assessed in rats with heat stroke. Heat stroke was induced by exposing the urethane-anesthetized rats to a high ambient temperature (42 degrees C). Damage to the hypothalamus, corpus striatum, cortex or thalamus was scored on a scale of zero to three modified from the grading system of Pulsinelli and colleagues in which: 0 = normal, 1 = few neurons damaged, 2 = many neurons damaged, and 3 = all neurons damaged. During the onset of heat stroke, as compared to those of normothermia controls, the heat stroke rats displayed a higher value of colonic temperature or neuronal damage score, as well as a lower value of local cerebral blood flow or mean arterial blood pressure. In addition, compared to those of normothermic, control rats, the heat stroke rats had increased interleukin-1 and tumor necroting factor production in the diencephalon, brain stem and cortex. The heat stroke-induced neuronal damage and diminished local cerebral blood flow in different brain structures, as well as the systemic hypotension, were attenuated in animals pretreated with IL-1ra (200 micrograms/kg, iv) 30 min before the onset of heat stroke. The results indicate that IL-1ra attenuates the heat stroke-induced cerebral neuronal damage by reducing cerebral ischemia in rats.

Analysis of the expression of Fas-L in nasopharyngeal carcinoma tissues.

Nasopharyngeal carcinoma (NPC) is an epithelial cancer with a high incidence in Southeast Asia. How it escapes attack from the host immune system is not fully understood. Recently, pieces of evidence show that Fas-ligand (Fas-L)-mediated apoptosis may be involved in immune privilege of tumours. To determine whether a similar mechanism may exist in NPC, the expression of Fas-L was analysed. Biopsy specimens of the nasopharynx were taken from 27 NPC patients. Histologically, they were either non-keratinizing or undifferentiated carcinomas. Nasopharyngeal biopsies of 11 other patients that proved to have no tumour served as control. The transcripts of Fas-L were detected by reverse transcription-polymerase chain reaction. Localization of Fas-L protein was performed with immunohistostaining using an antibody recognizing human Fas-L. All nasopharyngeal tissues have a similar amount of transcripts of Fas-L. However, the Fas-L protein was detected exclusively on the cell surface of malignant epithelial cells of NPC. The present findings suggest that Fas-L protein may be involved in evading immune attack of NPC.

Genetic alterations in oral squamous cell carcinoma of young adults.

The underlying molecular abnormalities associated with head and neck squamous cell carcinoma in young adults (< 40 years) are unknown. We analyzed DNA extracted from paired microdissected samples of normal squamous epithelia and invasive oral squamous cell carcinomas from 36 young adults at microsatellite loci commonly found in older patients and correlated the results with clinicopathologic parameters and outcome. Our results showed that 30 of the 36 (83%) tumors manifest loss of heterozygosity (LOH) in at least one marker. Microsatellite instability was manifested in only six tumors (< 17%). The highest incidences of alterations were noted at markers D9S168 (9p23-22), TP53 (17p13), and D17S799 (17p11) on the short arms of chromosomes 9 and 17. In general, the incidences of LOH at 3, 9 and 17p regions in young adults were similar to those found in older patients. No correlation between LOH at chromosomes 3, 9, and 17p and clinicopathologic parameters was found. Our study indicates that chromosomal regions with frequent genetic alterations involved in young adult squamous tumorigenesis are similar to those reported in older patients. Further studies of other chromosomes in this population are underway to define the novel molecular features of these tumors.