Objective Application of auditory brainstem response (ABR) in the study on the relationship of neonates with hypoxic-ischemic encephalopathy (HIE) and the children with hearing loss and auxiliary determine the prognosis of encephalopathy. Methods We prospectively selected neonates diagnosed as HIE in the department of neonatology of the Chengdu Women and Children Central Hospital from January, 2006 to June, 2008. Neonatal ABR was tested and the prognosis of neonates were observed through 3-year followed up in order to analyze the relationship between HIE severity and the severity of hearing handicap and the relationship between the severity of hearing handicap and prognosis. Statistical analysis was performed using SPSS 18.0. χ2 test was used to compare the rate between groups. Results 40 cases involving 80 ears were included, of which 33 cases accomplished the 3-year follow-up for prognosis. The results showed that, 86.3% HIE neonates had hearing handicap (mainly mild hearing loss, 40.0%). Medium-severe HIE groups had more serious hearing handicap than Mild HIE group with a statistical significance (continuity correction χ2=7.383, P=0.007). ABR results showed that, mild HIE is mainly manifested as I wave PL prolonged or poorly differentiated, accounting for 78.1%; medium - severe HIE are mainly manifested as III and V wave PL prolonged central segment abnormalities, accounting for 95.8%; the hearing threshold no more than 60 dB group had better prognosis than the hearing threshold more than 60 dB group prognosis (Fisher exact probability P=0.001). Conclusion ABR reflects that HIE severity and was positively related to the severity of hearing handicap. The more serious hearing loss in neonates is, the worse prognosis the neonates have. ABR can be used to assist the assessment of the prognosis of neonatal HIE.
摘要:目的:探讨卡配因抑制剂3(MDL28170)对新生大鼠缺氧缺血性脑损伤(HIBD)神经细胞凋亡的影响。方法:建立新生SD大鼠HIBD模型,治疗组于缺养缺血后即刻、2 h、4 h腹腔内注射MDL28170,对照组及手术组同时予生理盐水。缺氧缺血后24 h用免疫组化方法观察大脑皮质及海马CA1区Caspase3 蛋白表达、TUNEL法检测细胞凋亡,观察组织病理改变并计算海马神经元死亡数,透射电镜观察细胞超微结构。结果:缺氧缺血后24 h缺血侧大脑皮质及海马CA1区Caspase3和TUNEL阳性细胞数较对照组明显增加,透射电镜证实有凋亡细胞;MDL28170可减少阳性细胞数量,抑制神经元死亡,差异有显著性(Plt;0.05)。结论:MDL28170可通过抑制神经凋亡而对新生大鼠HIBD具有一定保护作用。Abstract: Objective: To investigate the effect of (Calpain inhibitor3) MDL28170 on neural apoptosis in a neonatal model of hypoxicischemic brain damage (HIBD). Methods: A neonatal model of HIBD was established, 7dayold SD rats were divided into three groups. The treatment group received MDL28170(ip) at 0 h,2 h,4 h after HI, whereas the other two groups were administered normal saline simultaneously. The expression of caspase3 (by immunohistochemistry), neural apoptosis (by TUNEL) in cortex and hippocampus ipsilateral to the insult were observed 24 h after HI; hippocampal CA1 neural loss and electromicroscopic changes were assessed at the same time. Results: Apoptotic body was observed by electromicroscopy. Caspase3 positive cells and apoptotic cells increased significantly in the ipsilateral cortex and hippocampal CA1 region compared to the control, and MDL28170 reduced the number of positive cells, attenuated CA1 neural loss with significance (Plt;0.05). Conclusion: It is suggested that MDL28170 may protect the brain of neonatal rats after HIBD by suppressing neural apoptosis.
Objective To investigate the expressions of hypoxia-inducible factor-1α (HIF-1α) and caudal homeobox gene 2 (CDX2) in colorectal adenocarcinoma, and the relationships between them and the clinicopathologic factor of colorectal adenocarcinoma. Methods The expressions of HIF-1α and CDX2 were detected by immunohistochemistry in 62 specimens of colorectal adenocarcinoma and 20 specimens of normal colorectal mucosa tissue. The correlation between the expressions of HIF-1α and CDX2 was analyzed by Spearman rank correlation analysis. Results The positive rates of HIF-1α expression in normal colorectal mucosa tissue and colorectal adenocarcinoma were 5.0% (1/20) and 62.9% (39/62), CDX2 were 95.0% (19/20) and 69.4% (43/62), the differences of positive rate between different tissues were significant (Plt;0.05). In colorectal adenocarcinoma, the expression of HIF-1α or CDX2 was related to tumor differentiation, lymph node metastasis, and Dukes staging (Plt;0.05). There was a negative correlation between HIF-1α and CDX2 expressions in colorectal adenocarcinoma (r=-0.293 2,Plt;0.05). Conclusions The up-regulation of HIF-1α and down-regulation of CDX2 may be involved in the genesis of colorectal adenocarcinoma, and there is a negative correlation between the two kinds of protein. HIF-1α may participate in modulation of CDX2 expression and lead to accelerate the progression of colorectal carcinoma.
Objective To summarize the advance of bioenergetic metabolic mechanisms of cancer cell. Methods Literatures about the recent studies on the bioenergetic metabolic mechanisms of cancer cell were reviewed.Results Cancer cells required a steady source of metabolic energy in order to continue their uncontrolled growth and proliferation. Accelerated uptake of glucose and glycolysis was one of the biochemical characteristics of hypoxia cancer cells. Glucose transport and metabolism were essential for the survival of tumor cells, leading to poor prognosis. Conclusions The studies on relationships between hypoxia-inducible genes and cancer have come a new understanding of the bioenergetic metabolic mechanisms of cancer cell, become new and important supplementary means of diagnosis and treatment of cancer, and enhanced existing strategies so that the treatment could be more rationally applied and personalized for cancer patients.
Objective To elucidate whether glucose transporters-4 (GLUT-4) takes part in glucose uptake of mesenchymal stem cells (MSCs) and whether Akt gene improves translocation and expression of GLUT-4 in MSCs under hypoxic environment ex vivo. Methods MSCs, transfected by Akt gene and no, were cultured with normoxia (5% CO2) or hypoxia (94%N2, 1%O2 and 5% CO2) at 37 ℃ for 8 h. Glucose uptake was assayed by using radiation isotope 2-[3H]-deoxy-Dglucose (3H-G) and the expression of GLUT-4 protein and mRNA was assayed by immunocytochemistry, Western blot and RT-PCR, respectively. Results ①3 H-G intake of MSCs was significantly increased in hypoxiatransfection group than that in hypoxia-non-transfection 〔(1.39±0.13) fold, P<0.05〕, but which was lower than that in normoxia-non-transfection group, P<0.05. ②GLUT-4 was expressed by MSCs under any conditions. Compared with normoxia-non-transfection group, hypoxia decreased the expressions of GLUT-4 mRNA and protein significantly (P<0.05). ③Compared with hypoxianontransfection group, the expression of GLUT-4 〔mRNA(1.756±0.152) fold, total protein in cell (1.653±0.312) fold, protein in plasma membrane (2.041±0.258) fold〕 was increased in hypoxia-transfection group significantly (P<0.05), but which was lower than that in normoxianontransfection group (P<0.05). ④There was significantly positive relation between 3H-G intake and GLUT-4 protein expression in plasma membrane (r=0.415, P=0.001).Conclusion GLUT-4 may take part in glucose uptake of MSCs, and the capability of Akt gene to improve MSCs anti-hypoxia may be finished by its role in increasing the expression and translocation of GLUT-4.
Objective To compare the effects of oxygen therapy and local pressurization in alleviating plateau hypoxia at high altitude. Methods Forty-five healthy male soldiers were investigated at an altitude of 3992 meters. The subjects were randomly divided into three groups, ie. an oxygen inhalation group, a single-soldier oxygen increasing respirator ( SOIR) group and a BiPAP group. The oxygen inhalation group was treated with oxygen inhalation via nasal catheter at 2 L/ min. SOIR was used to assist breath in the SOIR group. The BiPAP group were treated with bi-level positive airway pressure ventilation, with IPAP of 10 cm H2O and EPAP of 4 cmH2 O. PaO2, PaCO2, SpO2 and heart rate were measured before and 30 minutes after the treatment. Results There were continuous increase of PaO2 from ( 53. 30 ±4. 88) mm Hg to( 58. 58 ±5. 05) mm Hg and ( 54. 43 ±3. 01) mm Hg to ( 91. 36 ±10. 99) mm Hg after BiPAP ventilation and oxygen inhalation, respectively ( both P lt; 0. 01) . However, the PaO2 of the SOIR group was decreased from( 56. 00 ±5. 75) mm Hg to ( 50. 82 ±5. 40) mm Hg( P lt; 0. 05 ) . In the other hand, the PaCO2 was increased from ( 30. 41 ±1. 51) mmHg to ( 32. 56 ±2. 98) mm Hg in the oxygen inhalation group ( P lt; 0. 05) , declined from( 28. 74 ±2. 91) mm Hg to ( 25. 82 ±4. 35) mm Hg in the BiPAP group( P lt;0. 05) ,and didn’t change significantly from( 28. 65 ±2. 78) mm Hg to ( 29. 75 ±3. 89) mmHg in the SOIR group ( P gt;0. 05) . Conclusions Both BiPAP ventilation and oxygen inhalation can alleviate plateau hypoxia by improving PaO2 at 3992 meter altitude while SOIR has no significant effect.
Objective To extract and identify primary culture rat pulmonary arterial smooth cells ( PASMCs) , and investigate the effects of hypoxia on the proliferation of PASMCs. Methods Rat PASMCs were separated by the method of tissue block anchorage, and the cellular morphology was observed under light microscope. The cells were identified by projection electron microscopy, and α-smooth muscle actin ( α-SMactin)in the cells was identified by immunohistochemistry and immunofluorescence. The primary cultured PASMCs were exposed to normoxic and/ or hypoxia condition for 2, 6, 12, 24, 48 hours respectively, thenMTT assay and PCNA ( proliferating cell nuclear antigen) immunohistochemistry were used to detect the proliferation of PASMCs. Results The cells tended to be long spindle and grew in the “peak-valley”mode under light microscope. Immunology results showed that endochylema was stained in brownish yellow, and the positive rate was beyond 96% . There were dense patch, dense body and many filaments in endochylema under projection electron microscopy. MTT assay demonstrated that the A values of PASMCs expose to hypoxia were higher than that of nomoxia. Comparing with normoxia, the A values of PASMCs exposed to hypoxia increased after 12 hours ( P lt;0. 05) , significantly increased after 24 hours ( P lt;0. 01) . Compared with 2 hours’exposure to hypoxia, the A values increased after 12 hours( P lt; 0. 05) , markedly increased after 24 hours ( P lt; 0. 01 ) , which after 48 hours was similar with 24 hours. The result of PCNA immunohistochemistry was consistent with that of MTT. Conclusions The tissue explants adherent method is simple and convenient, and can easily obtain rat PASMCs with high purity and stability. Hypoxia canpromote the proliferation of PASMCs.