Renal B-lymphoblastic lymphoma with hematuria as the first symptom diagnosed in urine cytology: A case report and literature review.

Cytological examination of urine sediment is a helpful diagnostic tool for identifying renal involvement by hematological malignancies. We present the case of a 47-year-old man who was diagnosed with extranodal B-lymphoblastic lymphomas after presenting with gross hematuria as his first symptom. The presence of lymphoma cells in the urine led to a diagnosis confirmed through an immunophenotypic study using cell block sections of urine centrifuge sediment and core needle biopsy histology of the right renal pelvis mass. This case highlights the usefulness of a urine cytological study in diagnosing lymphoma involvement in the genitourinary tract. Furthermore, this paper reviews relevant literature on diagnosing lymphoma involvement from urine sediment.

Some pleomorphic adenomas of the breast share PLAG1 rearrangements with the analogous tumour of the salivary glands.

AIMS: Pleomorphic adenoma (PA) of the breast, and especially its malignant transformation, is extremely rare and represents a diagnostic pitfall. Molecular alterations in this entity have not been investigated. We aimed to examine the clinicopathological features of our breast PAs and perform molecular analysis. METHODS AND RESULTS: Seven cases of breast PA, including two cases of carcinoma ex PA, were analysed. PLAG1 and HMGA2 gene rearrangements were assayed by fluorescence in-situ hybridisation (FISH) and RNA sequencing (RNA-Seq), respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to verify RNA sequencing results. All seven cases of breast PA occurred in women. The histological features were similar to the analogous tumour in salivary glands, including a dual epithelial-myoepithelial component and negativity of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry. Of the two cases with carcinoma ex PA, one demonstrated minimal invasion and one was extensively invasive. PLAG1 rearrangements were identified in two cases (28.6%), but no rearrangements of HMG2A were found. A novel fusion product in PAs, TRPS1-PLAG1, was identified in one case. No patients had recurrence or metastasis with a follow-up period of 6-158 months. CONCLUSIONS: Breast PA is rare, but it is an important differential diagnosis of breast pathology with the potential to develop carcinoma ex PA. We report a novel TRPS1-PLAG1 fusion gene in breast PA.

Alterations of Hematologic and Hematopoietic Parameters in Mice Exposed to Pulsed Electromagnetic Field.

Effects of pulsed electromagnetic field (PEMF) on hematology and hematopoiesis might vary with different PEMF parameters. The purpose of this study was to evaluate the possible effects of PEMF exposure at different pulses on hematologic and hematopoietic parameters in mice. Groups of male BALB/c mice were whole body exposed or were sham exposed (control) to PEMF at 100, 1000, and 10000 pulses. After PEMF exposure, blood samples and bone marrow cells of mice were collected for hematologic examinations, bone marrow nucleated cell counting, colony-forming units of granulocyte-macrophage (CFU-GM) colony assay, and serum granulocyte-macrophage colony-stimulating factor (GM-CSF) assay. Compared with the control group, white blood cells (WBC) and lymphocytes (LYM) in the 100 and 1000 pulses exposed groups were significantly increased but not changed in the 10000 pulses exposed group. Red blood cells (RBC), hemoglobin (HGB), and platelets (PLT) were not changed in all exposed groups. There was no significant difference in mouse bone marrow nucleated cell number between the control group and each exposed group 7 days after PEMF exposure. The CFU-GM clone number of bone marrow cells and serum GM-CSF level were significantly increased in the 100 and 1000 pulses exposed group but not changed in the 10000 pulses exposed group. Our results indicated that the PEMF exposure at fewer pulses may induce statistically significant alterations in some hematologic and hematopoietic parameters of mice but no changes can be found in the more pulses PEMF-exposed groups.

MET-overexpressing myxofibrosarcoma frequently exhibit polysomy of chromosome 7 but not MET amplification, especially in high-grade cases: clinical and pathological review of 30 myxofibrosarcoma cases.

BACKGROUND: Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas. Previous studies have shown that MET protein overexpressed in MFS patients and can serve as a prognostic factor. The reasons for MET protein overexpression include amplification of the MET gene, which is located on chromosome 7q. Triggered by an index case harboring chromosome 7 polysomy rather than MET gene amplification in myxofibrosarcoma, we investigated chromosome 7 polysomy in more cases. METHODS: Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed in 30 MFS cases (including 2 epithelioid variant) to detect the expression of MET protein and gene status. RESULTS: MET was overexpressed in 14 cases out of 30, while thirteen cases were in higher FNCLCC grades (Grade 2-3). FISH showed that 11 cases having 3 signals on average of Met and more than 3 signals (Mean: 4.6) of centromere 7q (CEP7q). The MET/CEP7 ratio was about 0.65 on average, suggesting that chromosome 7 polysomy, rather than Met gene amplification, leading to the overexpression of MET protein in MFS. MET overexpression and chromosome 7 polysomy are positively correlated with higher Ki-67 index and higher grade and might have a high risk of local recurrence and metastasis. CONCLUSIONS: It might reveals another explain of MET overexpression in myxofibrosarcoma, providing a clue for the therapy of MFS.

EZH2 overexpression in different immunophenotypes of breast carcinoma and association with clinicopathologic features.

BACKGROUND: Enhancer of zest homolog 2 (EZH2), a histone 3 methyltransferase, is associated with aggressive behavior of many tumors and is a promising target of molecular therapy. METHODS: To better elucidate the relevance of EZH2 in breast cancer subtypes, we evaluated EZH2 expression in 226 invasive breast carcinomas with four distinct immunophenotypes and in association with clinicopathological features. RESULTS: Of these cases, 138 (61.1 %) were defined as EZH2-overexpressing with a multiplicative score > 3. EZH2 expression was inversely related to the status of ER and PR (Chi-square, p < 0.001), and it was significantly associated with HER2 positivity, high proliferative index, and high histologic grade (Chi-square, p < 0.05). ER-positive breast carcinoma with low proliferative index (Ki67 < 14 %) showed the lowest expression and triple-negative breast carcinoma showed the highest overexpression of EZH2, 18.5 % (10/54) versus 90.9 % (50/55) (Chi-square, p < 0.001). Intriguingly, 88 % (44/50) cases of grade 3 triple-negative breast carcinoma showed uniformly strong EZH2 expression with a multiplicative score of 9. The percentage of EZH2 overexpression in ER-positive breast carcinoma with a high proliferative index or HER2-positive cases were 61.2 and 74 %, respectively. Furthermore, EZH2 expression was significantly elevated in high-grade DCIS compared to benign lesions (90 % versus 0, p < 0.001). However, there is no association between EZH2 expression and the status of histone 3 lysine 27 trimethylation or other clinicopathologic features. CONCLUSION: In summary, triple-negative breast carcinoma showed the highest overexpression of EZH2. EZH2 overexpression is associated aggressive pathologic features including high nuclear grade, high proliferative index, and positivity of HER2 of breast carcinoma.

Effects of pulsed electromagnetic field on differentiation of HUES-17 human embryonic stem cell line.

Electromagnetic fields are considered to potentially affect embryonic development, but the mechanism is still unknown. In this study, human embryonic stem cell (hESC) line HUES-17 was applied to explore the mechanism of exposure on embryonic development to pulsed electromagnetic field (PEMF) for 400 pulses at different electric field intensities and the differentiation of HUES-17 cells was observed after PEMF exposure. The expression of alkaline phosphatase (AP), stage-specific embryonic antigen-3 (SSEA-3), SSEA-4 and the mRNA level and protein level of Oct4, Sox2 and Nanog in HUES-17 cells remained unchanged after PEMF exposure at the electric field intensities of 50, 100, 200 or 400 kV/m. Four hundred pulses PEMF exposure at the electric field intensities of 50, 100, 200 or 400 kV/m did not affect the differentiation of HUES-17 cells. The reason why electromagnetic fields affect embryonic development may be due to other mechanisms rather than affecting the differentiation of embryonic stem cells.

Effects of PEMF exposure at different pulses on osteogenesis of MC3T3-E1 cells.

OBJECTIVE: Pulsed electromagnetic fields (PEMFs) were considered to be a factor which may affect osteogenesis of osteoblasts, but the effects were diverse with different PEMF parameters. The aim of the current study is to explore the effects of exposure to PEMFs at different pulse number on osteogenesis of osteoblasts. DESIGN: The mouse osteoblast-like MC3T3-E1 cells were exposed to 0, 400 or 2800 pulses 400kV/m PEMF and the proliferation, differentiation and mineralization of cells were observed after PEMF exposure by the methods of MTT, biochemical measurement, real-time PCR and Alizarin Red assay. RESULTS: Compared with 0 pulses groups, the growth curve, alkaline phosphatase (ALP) activity, mRNA level of osteocalcin (OCN) and mineralized nodule formation of MC3T3-E1 cells did not change after 400 pulses PEMF exposure, but decreased after 2800 pulses PEMF exposure. It suggested that under our experimental conditions, only 2800 pulses 400kV/m PEMF exposure can suppress the proliferation, differentiation and mineralization of MC3T3-E1 cells, but 400 pulses 400kV/m PEMF exposure cannot. CONCLUSIONS: Pulse number is another involved parameter which may influence the effects of PEMF on osteogenesis of osteoblasts.

Effects of electromagnetic pulse on serum element levels in rat.

Electromagnetic pulse (EMP) was a potentially harmful factor to the human body, and a biological dosimetry to evaluate effects of EMP is necessary. Little is known about effects of EMP on concentration of macro and trace elements in serum so far. In this study, Sprague-Dawley rats were randomly divided into 50-kV/m EMP-exposed group (n = 10), 100-kV/m EMP-exposed group (n = 10), 200-kV/m EMP-exposed group (n = 40), and the sham-exposed group (n = 20). The macro and trace element concentrations in serum were examined at 6, 12, 24, and 48 h after EMP exposure at different electric field intensities. Compared with the sham-exposed groups, the concentration of sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), zinc (Zn), copper (Cu), iron (Fe), selenium (Se), and manganese (Mn) in rat serum was not changed significantly within 48 h after 200 pulses of EMP exposure at electric field intensity of 50, 100, and 200 kV/m although the K level was decreased and the Ca level was increased with the electric field intensity of EMP increasing. In addition, there was a tendency that the Zn level was decreased with the time going on within 48 h after EMP exposure. Under our experimental conditions, EMP exposure cannot affect the concentration of macro and trace elements in rat serum. There was no time-effect or dose-effect relationship between EMP exposure and serum element levels. The macro and trace elements in serum are not suitable endpoints of biological dosimetry of EMP.

Osthole protects lipopolysaccharide-induced acute lung injury in mice by preventing down-regulation of angiotensin-converting enzyme 2.

The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Angiotensin converting enzyme 2 (ACE2) plays a protective role in acute lung injury. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to have anti-inflammatory effect, but the effect of osthole on the ALI is largely unknown. The aim of this study is to explore whether and by what mechanisms osthole protects lipopolysaccharide(LPS)-induced acute lung injury. Herein, we found that osthole had a beneficial effect on LPS-induced ALI in mice. As revealed by survival study, pretreatment with high doses of osthole reduced the mortality of mice from ALI. Osthole pretreatment significantly improved LPS-induced lung pathological changes, reduced lung wet/dry weight ratios and total protein in BALF. Osthole also inhibited the release of inflammatory mediators TNF-α and IL-6. Meanwhile, osthole markedly prevented the loss of ACE2 and Ang1-7 in lung tissue of ALI mice. ACE2 inhibitor blocked the protective effect of osthole in NR 8383 cell lines. Taken together, our study showed that osthole improved survival rate and attenuated LPS-induced ALI and ACE2 may play a role in it.

Primary epithelioid hemangioendothelioma in the clival region: a case report and literature review.

Epithelioid hemangioendothelioma (EHE) is a rare and low-grade vascular tumor, which usually occurs in the soft tissue, liver, breast, lung and skeleton. Here we submit a case with EHE of the clival region. A 58-year-old woman was admitted with a medical history of 3 months headache and 1 month visual deterioration. MRI revealed a well-circumscribed mass of 4.0 cm × 3.0 cm with bony invasion. The tumor was subtotally removed in a piecemeal fashion. Histologically, the tumor was composed of epithelioid cells with eosinophilic cytoplasm and intracytoplasmic vacuoles. Immunohistochemically, the tumor cells were positive for the markers CD31, CD34, factor VIII and vimentin. The pathological result was interpretated as EHE of the clival region. EHE is an uncommon vascular tumor, which is rarely seen in the clival region. Definitive diagnosis depends on histopathologic and immunohistochemical features.

Effects of reactive oxygen species scavenger on the protective action of 100% oxygen treatment against sterile inflammation in mice.

Sepsis/multiple organ dysfunction syndrome (MODS) is a major cause of high mortality in the intensive care unit. We have recently reported that 100% oxygen treatment is beneficial to mice with zymosan-induced sterile inflammation by increasing antioxidant enzymatic activities. Yet, the use of hyperoxia is hindered by concerns that it could exacerbate organ injury by increasing free radical formation. It is believed that systemic inflammation and overproduction of reactive oxygen species (ROS) contribute to the mechanism underlying sepsis/MODS. A ROS scavenger has been proven to protect against sepsis/MODS in some animal models. Therefore, we hypothesized that ROS scavenger pretreatment might enhance the protective action of 100% oxygen treatment against zymosan-induced sterile inflammation in mice. In the present study, we showed that 100% oxygen treatment prevented the abnormal changes in serum biochemical parameters, tissue oxygenation, and organ histopathology, and improved the 14-day survival rate in zymosan-stimulated mice, indicating that 100% oxygen treatment had a protective action on sterile inflammation. We found that pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea) abolished this protective action of 100% oxygen treatment. We also showed that 100% oxygen treatment decreased the levels of serum proinflammatory cytokines (TNF-alpha, IL-6, and high-mobility group box 1), increased the level of serum anti-inflammatory cytokine (IL-10), and upregulated the activities of serum and tissue antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in zymosan-stimulated mice, which were reversed by the pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea). We thus conclude that ROS scavenger pretreatment partly abolishes the protective effects of 100% oxygen treatment on sterile inflammation in mice by regulating inflammatory cytokines as well as antioxidant enzymes.

100% oxygen inhalation protects against zymosan-induced sterile sepsis in mice: the roles of inflammatory cytokines and antioxidant enzymes.

Sepsis is a leading cause of death in patients with critical illness. However, there is no effective therapy available. Recent studies have suggested that ventilation with 100% oxygen (Oxy) can improve the survival rate and organ function in several shock models. However, a lot of work is necessary to be done before its clinical application, and its detailed mechanism remains to be clarified. In the present study, we showed that 100% Oxy inhalation for 2 or 3 h starting at 4 and 12 h after zymosan (ZY) injection, respectively, prevented the abnormal changes of serum biochemical parameters, tissue oxygenation, and organ histopathology, and improved the 14-day survival rate from 10% to 60% to 80% in mice. However, 100% Oxy inhalation for 1 or 4 h starting at the same time points has little preventive effects. We also showed that twice 100% Oxy inhalation for 2 or 3 h attenuated the increase of inflammatory cytokines and precluded the downregulation of antioxidant enzymatic activities. We further showed that the therapeutic time window of Oxy treatment against sterile sepsis was less than 12 h after ZY injection. We conclude that 100% Oxy inhalation for 2 or 3 h starting 4 and 12 h after ZY injection, respectively, protects against ZY-induced sterile sepsis via regulating inflammatory cytokines and antioxidant system in mice. The present results may provide a potential cue for developing more effective therapeutic strategies for patients with sepsis.

Effects of electromagnetic pulse on bone metabolism of mice in vivo.

OBJECTIVE: To study the effects of electromagnetic pulse (EMP) on bone metabolism of mice in vivo. METHODS: Twenty-four male BALB/c mice were divided into a control group and 2 experimental groups (n=8). The whole-body of mice in experimental groups were exposed to 50 kV/m and 400kV/m EMP, 400 pulses daily for 7 consecutive days at 2 seconds intervals. Alkaline phosphotase (ALP) activity, serum calcium concentration and osteocalcin level and trabecular bone volume (BV/TV, %) were measured immediately after EMP exposure by biochemical, ELISA and morphological methods. RESULTS: The ALP activity, serum calcium concentration and osteocalcin level and BV/TV in experimental groups remained unchanged after EMP exposure. Conclusion Under our experimental conditions, EMP exposure cannot affect bone metabolism of mice in vivo.

[Change of oxygen free radical in reversing multidrug-resistance of human leukemic cell line HL-60/ADM by cyclosporin A].

This study was aimed to evaluate the reversed effects of cyclosporin A (CsA) on multidrug resistance (MDR) of human leukemic cell line HL-60/ADM, and to investigate the relationship of the oxygen free radical content between HL-60/ADM cells and the reversed HL-60/ADM cells (HL-60/ADM + CsA). The cytotoxicity and the reversed effects of CsA on multidrug resistance of human leukemic cell line HL-60/ADM were studied by MTT, flow cytometry (FCM) and immunohistochemical assay; the oxygen free radical for HL-60/ADM and HL-60/ADM + CsA cell lines were detected by colorimetric method. The results showed that the CsA less than 4 microg/ml had no significant cytotoxicity on HL-60/ADM, while the cytotoxicity was rised with CsA concentration increasing; And CsA (4 microg/ml) combined with ADM (1 microg/ml) could obviously restrain the growth of HL-60/ADM cells (p < 0.001). The P-gp expression of HL-60/ADM decreased obviously after exposure to CsA (4 microg/ml) for 72 hours, at the same cell conditions, MDA concentration of the reversed groups (HL-60/ADM + CsA cells) was higher than that of the control groups (HL-60/ADM cells) (p < 0.05), while the levels of SOD and GSH in the reversed groups were significantly lower than that in control groups (p < 0.001). It is concluded that MDR of HL-60/ADM can be reversed effectively by low dose of CsA, the level of oxygen free radical increases and the activity of antioxidants decreases in the reversed cells. Oxygen free radicals may be involved in this reverse process, which thereby lead to the cell death.

[The examination of ultraweak luminescence of HL-60 cells and adriamycin-resistant HL-60/ADM cells].

AIM: To explore the relationship between the ultraweak luminescence and adriamycin resistantance in human leukemic cells (HL-60) and human adriamycin resistant leukemic cells (HL-60/ADM). METHODS: MTT colorimetry, flow cytometry (FCM), growth curve and immunohistochemical staining were used to detect the sensitivity of HL-60 and HL-60/ADM cells to ADM, the change of cell cycle and the expression of P-glycoprotein(P-gp170). The intensity of the ultraweak luminescence of HL-60 cells and HL-60/ADM cells was examined by the IFFM-D chemiluminescence instrument. RESULTS: The sensitivity of HL-60/ADM cells to ADM was distinctly lower than that of HL-60 cells. The percentage of HL-60/ADM cells in G(0)/G(1) was 44.80%+/-1.97% and that in G(2)/M phase was 9.90%+/-0.27%, which was both higher than that of HL-60 cells. The percentage of HL-60/ADM cells in S phase was 45.30%+/-1.93%, which was lower than that of HL-60 cells. The doubling time of HL-60/ADM cells was 1.8 times as long as that of HL-60 cells. The expression of P-gp170 was positive in HL-60/ADM cells but negative in HL-60 cells.Treated with 10(-4) mol/L luminol and 3 mL/L H(2)O(2) and under four different cell concentration (8x10(7)/L,1x10(8)/L,1.26x10(8)/L, 2.73x10(8)/L), the intensity of ultraweak luminescence of HL-60/ADM cells was distinctly lower than that of HL-60 cells (P<0.05). CONCLUSION: The lower sensitivity to ADM, longer doubling time and the expression of P-gp170 showed the drug resistance of HL-60/ADM cells. With the obtaining of drug resistance, ultraweak luminescence intensity was lower in HL-60/ADM cells than that of HL-60 cells. It showed that the decreasing of intensity of ultraweak luminescence could be an index of examining drug-resistantce of tumor cells.

Genetic diversity of five Kobresia species along the eastern Qinghai-Tibet plateau in China.

Plants of the genus Kobresia are alpine grass species of high ecological and economic importance. Vegetative growth is the dominant means of reproduction for the Kobresia. Studies suggest that substantial vegetative growth can reduce genetic diversity and renders populations less able to buffer changing and extreme conditions. Kobresia are dominant species in the Qinghai-Tibet plateau in China where they face harsh conditions and frequent disturbance. The genetic diversity of five Kobresia species (K. humilis, K. royleana, K. kansuensis , K. tibetica and K. setchwanensis) from the Qinghai-Tibet plateau was assessed. The results reveal high genetic diversity at the population level for all of the species and there does not appear to be a relationship between altitude and genetic diversity. AMOVA analysis shows that most genetic variability resides among individuals within populations, whereas only a minor portion is found among populations. Of the five species, K. royleana and K. kansuensis have the highest levels of gene flow and the lowest genetic differentiation. While K. setchwanensis has the lowest gene flow and the greatest genetic differentiation. The level of gene flow between populations and the mating system play a critical role in the genetic structure of these Kobresia populations. Despite the predominance of vegetative growth enough sexual reproduction occurs to maintain the relatively high genetic diversity in Kobresia populations.