Objective To investigate the mechanism responsible for the malignant progressionof meningiomas at the protein level using tissue microarray technique. Methods Twenty-twointracranial meningioma tissue microarrays were constructed, each containing the tissues of 42 benign, 18atypical, and 19 anaplastic meningiomas. Immunohistochcmistry of the microarrays was performed induplicate with the antibodies of MYC, ARNT2, MDM2, AR, ER, PR, Ki-67, P53, survivin, CD34 andVEGF, respectively. Negative control microarrays were used throughout the experiment and breast cancertissue microarrays were used as the positive controls for ER and PR staining. SAS9.0 solfware was usedfor grading of the expression levels of the biomarkers according to the WHO grades of meningiomas.Results For each antibody, the duplicate tissue microarrays yielded uniform staining results invisualization of the protein distributions in the cytoplasm and nuclei, and the negative controls displayedno positive staining. The p53, AR, ER, PR and Ki-67 proteins were found only in the cell nuclei, MDM2in both the cytoplasm and nuclei, and ARNT2, CD34 and VEGF in the cytoplasm only. The c-MYC andsurvivin proteins were found mainly in the cytoplasm, and in some instances in both the cytoplasm andcell nuclei. Immunohistochemical staining for p53, AR, CD34, Ki-67 and MYC proteins showed strongcorrelations to the degree of malignancy of the meningioma (P<0.05). Conclusions Tissue microarrayand immunohistochemical techniques provide an efficient means for screening the specific biomatkers ofmeningiomas. The expressions of p53, AR, CD34, Ki-67 and MYC proteins are involved in the malignantprogression of meningioma, and these proteins may serve as important biomarkers for meningiomagrading at the protein level.

Objective To evaluate the effects of ulinastatin on hemorrhagic shock and resuscitation ( HS∕R)?induced acute lung injury in rats. Methods Fifteen SPF adult Sprague?Dawley rats, aged 2-3 months, weighing 300-400 g, were divided into 3 groups ( n=5 each) using a random number table:sham operation group ( group S ) , HS∕R group and ulinastatin group ( group U ) . Carotid arteries were cannulated for blood pressure monitoring and blood?letting. HS∕R was induced by blood?letting and maintained for 1 h, followed by resuscitation with autologous blood transfusion and infusion of normal saline. After cannulation of carotid arteries ( T0 ) , at 5 min after hemorrhagic shock ( T1 ) , before resuscitation ( T2 ) , at 5 min after the expected blood pressure was achieved following resuscitation ( T3 ) , and at 30 min, 1?5 h and 2?5 h after resuscitation ( T4?6 ) , arterial blood samples were collected for determination of interleukin?6 ( IL?6 ) and tumor necrosis factor?α ( TNF?α) concentrations ( by enzyme?linked immunosorbent assay) . Arterial blood samples were collected at T0 , T2 and T6 for blood gas analysis. The pH value, partial pressure of arterial carbon dioxide ( PaCO2 ) , HCO-3 and base excess ( BE) value were recorded, and oxygenation index ( PaO2∕FiO2 ) was calculated. Lungs were removed at T6 , and pulmonary specimens were obtained for examination of pathological changes which were scored, and nucleus was extracted for determination of nuclear factor?kappa B ( NF?κB ) p65 expression by enzyme?linked immunosorbent assay. Results Compared with group S, the pH values, HCO-3 , BE values and OI were significantly decreased, and PaCO2 , plasma IL?6 and TNF?α concentrations, expression of NF?κB p65 in lung tissues, and pathological scores were increased in U and HS∕R groups. Compared with group HS∕R, the plasma concentrations of IL?6 and TNF?α, expression of NF?κB p65 in lung tissues, and pathological scores were significantly decreased, and no significant changes were found in parameters of blood gas analysis in group U. Conclusion Although ulinastatin can alleviate HS∕R?induced acute lung injury, it is insufficient to improve lung oxygenation in rats.

Niemann-Pick disease type C (NPC) is a fatal,neurovisceral lipid storage disease,neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons,progressive neuronal loss,neurofibrillary tangles (NFTs) formation,and axonal spheroids (AS).Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC (npc mice).With a goal of elucidating the mechanisms underlying the lesion formation,we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2,cdk4,and cdk5 in lesion formation in young npc mice.Cytoskeletal lesions were detectable in npc mice at three weeks of age.Importantly,concomitant activation of cdc2/cyclin B 1 kinase and accumulation of a subsequently generated cohort of phospho-epitopes were detected.The activation of cdk4/cyclin D1 and cdk5/p25 kinases was observed during the fourth week of life in npc mice,and this activation contributed to the lesion formation.We concluded that the progression of cytoskeletal pathology in npc mice older than four weeks is accelerated by the cumulative effect of cdc2,cdk4,and cdk5 activation.Furthermore,cdc2/cyclin B1 may act as a key initial player one week earlier.Targeting cell cycle activation may be beneficial to slow down the NPC pathogenesis.

OBJECTIVE: To investigate the expression of Hypoxia inducible factor-1alpha (HIF-1alpha)and the Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) in human laryngeal carcinoma and their relationship. METHOD: The expression of HIF-1ALPHA and BNIP3 were detected by SP immunohistochemical method in 45 cases with laryngeal carcinoma tissues and 12 adjacent normal laryngeal tissue. RESULT: The expression of HIF-1alpha and BNIP3 were mainly in cytoplasm and nucleus. Their expression was higher in laryngeal tissue than in adjacent normal laryngeal tissue (P < 0.05). The expression of HIF 1alpha was positively related to that of BNIP3 in laryngeal carcinoma tissues (P < 0.05). CONCLUSION The high expression of HIF-1alpha and BNIP3 were closely related in laryngeal carcinomas, both of them played important role in the carcinogenesis and development of laryngeal carcinoma. HIF-1alpha might induce the expression of BNIP3. HIF-1alpha and BNIP3 might to be two potential therapeutic targets in laryngeal squamous, cell carcinomas.
Carcinoma, Squamous Cell ; metabolism ; pathology ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Membrane Proteins ; metabolism ; Proto-Oncogene Proteins ; metabolism

Objective To explore the effect of Fas/FasL pathway on fluoride.induced apoptosis in hurnan neumbla8toma SH-SY5Y cells.Methods The cell survival rate,percentage of apoptosis,and mRNA expression levels of Fas and FasL were measured respectively after the SH-SY5Y cells were exposed to O(control),20,40,80 mg/L sodium nuoride(NaF)for 24 hours/n vitro.Furthermore,the changes of the percentage of apoptosis and mRNA expression levels of Fas and FasL in 40 mg/L NaF-treated groups incubated with activaling or neutralizing anti-Fas antibody(CH11 or ZB4)also observed respectively.Results Compared with the control group(100.00%), the cell surval rates in 40,80 mg/L NaF-treated groups[(84.63±2.57)%,(69.04±5.63)%]were significandy lower(P<0.01).The percentage of apoptosis in 40,80 mg/L NaF.treated groups[(8.54±1.95)%.(17.94±2.71)%]were higher(P<0.05)than thal in the control group[(3.32±1.33)%],and increased with the dose of NaF.NaF could up-regulate Fas and FasL mRNA expression,and increased the Fas/β-actin [40 ms/L group (0.94±0.51),80 mg/L group(0.99±0.12)]and FasL/β-actin[40 mg/L group(0.96±0.42),80 mg/L group(0.99±0.24)] ratio,compared with the control[Eas/β-actin(0.50±0.33),FasL/β-actin(0.58±0.23)],both the difference had 8tatistical significances (P<0.05).NaF and CH I 1 had a synergisfic effect on apoptosis and mRNA expression levels of Fas and FasLL(F=32.89,18.46,.14.69,P<0.01)while NaF and ZB4 had an antagonistic effect (F=5.73,24.26,10.17,P<0.05 or<0.01).Conclusion NaF exposure can cause apoptosis in SH-Y5Y cells,and the Fas/FasL pmhway may play an important role in NaF-induced apoptosis.

OBJECTIVE: To determine the efficacy of endoscopic surgery in combination with long-acting somatostatin analogues (SSAs) in treating patients with growth hormone (GH)-secreting pituitary tumor. METHODS: We performed retrospective analysis of 133 patients with GH producing pituitary adenoma who underwent pure endoscopic transsphenoidal surgery in our center from January 2007 to July 2012. Patients were followed up for a range of 3-48 months. The radiological remission, biochemical remission and complication were evaluated. RESULTS: A total of 110 (82.7%) patients achieved radiological complete resection, 11 (8.2%) subtotal resection, and 12 (9.0%) partial resection. Eighty-eight (66.2%) patients showed nadir GH level less than 1 ng/mL after oral glucose administration. No mortality or severe disability was observed during follow up. Preoperative long-acting SSA successfully improved left ventricle ejection fraction (LVEF) and blood glucose in three patients who subsequently underwent success operation. Long-acting SSA (20 mg every 30 days) achieved biochemical remission in 19 out 23 (82.6%) patients who showed persistent high GH level after surgery. CONCLUSION: Endoscopic transsphenoidal surgery can biochemically cure the majority of GH producing pituitary adenoma. Post-operative use of SSA can improve biochemical remission.
Blood Glucose ; Follow-Up Studies ; Glucose ; Growth Hormone* ; Heart Ventricles ; Humans ; Mortality ; Pituitary Neoplasms* ; Retrospective Studies ; Somatostatin*

Objective To explore the relationship between intracellular calcium levels ([Ca2+]1) and reactive oxygen species (ROS) in sodium fluoride (NaF)-induced injury in human neuroblastoma SH-SY5Y cells. Methods The levels of [Ca2+]1 and ROS were measured in different exposed times(0,3,6,12,18,24 h) respectively after SH-SY5Y cells were exposed to 40 mg/L NaF in vitro, and the optimal expose time was selected. Furthermore, the changes of [Ca2+]1, ROS and LDH levels in 40 mg/L NaF-treated groups incubated with 38.23 mg/L BAPTA-AM or 380.40 mg/L ethylene glycol-bis-(beta-aminoethyl ether)-N, N, N', N'-tetraacetic acid (EGTA) or 16.32 mg/L N-acetyl-L-cysteine(NAC) also observed at the optimal expose time(12 h), respectively. Results At 3,6,12,18 and 24 h, [Ca2+]1 level(5620.0±226.3,4775.5±85.6,3312.3±87.5, 3047.0±75.0,2717.0±66.5) was significantly increased, and so was the ROS level(4449.53±324.61,7463.07±117.43,20 227.33±178.04,8817.56±200.13, 7975.61±92.90) except at 3 h, compared with 0 h(2115.0±24.0,4098.01±21.22, all P<0.05). The levels of [Ca2+]1 and ROS reached the peak at 3 h and 12 h, respectively. [Ca2+]1 and LDH levels in NaF-treated group [3279.5±94.0, (1057.50±64.35)U/L], NaF+NAC treated group[ 3583.0±350.7, (561.02±85.50)U/L], NaF+EGTA treated groups[3701.5±157.7, (1074.50±86.97)U/L], and BAPTA-AM treated group[2766.5±38.9, (521.43±40.80)U/L] had increased, compared with the control[2022.5±118.1, (186.97±8.73)U/L], the difference being statistically significant (P<0.05). ROS levels in NaF-treated group (19 003.04±332.34), and NaF+EGTA treated group(19 170.12±95.46) was higher than that in the controls(4060.98±145.66), the difference being statistically significant (P<0.05). NaF and NAC had antagonistic effect on ROS and LDH levels (F=976.11,43.54,P<0.05). And NaF and BAPTA-AM had antagonistic effect on [Ca2+]1, ROS and LDH levels (F=15.65,1515.53,115.00, P<0.05). Conclusions NaF-related calcium is released from the site of intracellular calcium storage, which induces ROS production, both of them caused cytotoxicity and the increase of LDH level in human neuroblastoma SH-SY5Y cells.

To establish a method for detecting microdialysis recovery of tetramethylpyrazine (TMP) and ferulic acid (FA) and investigating the influencing factors, providing the basis for further in vivo microdialysis experiments. The concentration of FA and TMP in dialysates were determined by high pressure liquid chromatography ( HPLC) and probe recovery were calculated respectively. The influence of the flow rates, medium concentration, temperature and in vivo probe stability on the recovery of FA and TMP were investigated by using concentration difference method (incremental method and decrement method). The recovery obtained by incremental method were similar to by decrement method. The in vitro recovery rate of FA and TMP decreased with the increase of 1-2.5 μL min(-1), and increased obviously with the temperature of 25-42 degrees C under the same conditions. The concentration of FA and TMP had no obvious effect on the probe recovery under the same flow rate. In addition, the recovery of TMP and FA remained stable and showed similar trends under the condition of four concentration cycles, indicating that the intra day reproducibility of the concentration difference method was good. The recovery of brain microdialysis probes in vivo 8 h maintained a relatively stable, but certain differences existed between different brain microdialysis probes, demonstrating that each probe was required for recovery correction in vivo experiment. Microdialysis sampling can be used for the local brain pharmacokinetic study of FA and TMP, and retrodialysis method can be used in probe recovery of FA and TMP in vivo.
Animals ; Brain ; metabolism ; Chromatography, High Pressure Liquid ; Coumaric Acids ; analysis ; isolation & purification ; pharmacokinetics ; Drugs, Chinese Herbal ; Humans ; Microdialysis ; methods ; Pyrazines ; analysis ; isolation & purification ; pharmacokinetics ; Rats

OBJECTIVETo study an epidemic of human lung plague fulminant from September to October, 2004 in Nangqian county, Qinghai province.

METHODSCases were diagnosed through data from epidemiological, clinical, bacteriological, serological and autopsy studies.

RESULTS14 patients were identified, ending up with 6 deaths and 8 cured. The first case was diagnosed as primary pesticemia late progressed to lung plague. 4 cases were transformed from pesticemia out of 13, leaving the 9 cases as primary lung plague. Situation was under complete control through routinely handling the plague focus.

CONCLUSIONThe first case was bitten by the infected fleas which parasitized the marmota preyed on a dog but later these fleas were brought into the tent by the dog. The others cases were infected through droplets or dust. Programs on monitoring and controling the amount of marmotas and fleas should to be strengthened to prevent the epidemics of plague in the area.

Adult ; Animals ; Biopsy ; Cattle ; China ; epidemiology ; Disease Outbreaks ; Dogs ; Female ; Health Education ; Humans ; Male ; Middle Aged ; Plague ; diagnosis ; epidemiology ; pathology ; transmission

Objective:To investigate the role and mechanism of miR-143 in the proliferation and migration of gastric cancer (GC) cells. Methods:Western blot was performed to detect the expression level of avian erythroblastosis oncogene B-3 (ERBB3) in GC tissues, paired non-cancerous tissues, and SGC7901 GC cells. RT-qPCR was conducted to determine the mRNA and miR-143 of ERBB3 quantita-tively. Bioinformatics tools were used to predict the target gene of miR-143. Luciferase reporter assay was carried out to confirm the predicted target gene. Transwell and EdU assays were applied to observe the migration and proliferation of SGC7901 GC cells transfect-ed with miR-143 mimics/inhibitor/NC mimics/inhibitor. Results:Compared with the expression levels of ERBB3 and miR-143 in the paired non-cancerous tissues, the expression level of ERBB3 was upregulated and the expression level of miR-143 was downregulated in GC tissues. In the prediction of the potential target gene, miR-143 could bind to a specific sequence of the 3′-untranslated regions (UTR) of the mRNA of ERBB3. This finding was supported by luciferase reporter assay results. In vitro, ERBB3 protein expression and cell migration and proliferation were suppressed significantly in the SGC7901 cells transfected with miR-143 mimics. By contrast, these processes were remarkably enhanced when the cells were transfected with miR-143 inhibitor. Conclusion:miR-143 can suppress the migration and proliferation of GC cells by downregulating the expression of ERBB3.