不同赋形剂氢氧化钙根管消毒效果的临床研究

目的比较生理盐水、碘甘油、樟脑对氯苯酚、樟脑对氯苯酚/碘甘油等赋形剂对氢氧化钙消毒根管效果的影响,以期为临床工作提供参考。方法选择单根管慢性根尖周炎患牙80颗,随机分成氢氧化钙加生理盐水、氢氧化钙加碘甘油、氢氧化钙加樟脑对氯苯酚、氢氧化钙加樟脑对氯苯酚/碘甘油等4组,观察封药1周后的临床疗效、封药1周前后的细菌学培养菌落数变化以及达到临床可充填的封药时间等评价指标。结果氢氧化钙加樟脑对氯苯酚/碘甘油组明显优于氢氧化钙加生理盐水、氢氧化钙加碘甘油、氢氧化钙加樟脑对氯苯酚组(P<0.01);在封药1周的临床疗效(评分差值)方面,氢氧化钙加生理盐水组、氢氧化钙加樟脑对氯苯酚组差异无统计学意义(P>0.05);在达到临床可充填封药时间上,氢氧化钙加碘甘油组、氢氧化钙加樟脑对氯苯酚组差异无统计学意义(P>0.05)。结论在生理盐水、碘甘油、樟脑对氯苯酚、樟脑对氯苯酚/碘甘油等赋形剂中,樟脑对氯苯酚/碘甘油可能是最为有效的赋形剂。     

Monoclonal antibody 12D5 inhibits eosinophil infiltration in the brain of Angiostrongylus cantonensis-infected BALB/c mice

Each of BALB/c mice was infected with 50 Angiostrongylus cantonensis larvae. One group of mice received an intraperitoneal injection of 50 μg 12D5 monoclonal antibody (mAb) against a 98 kDa antigen of adult worms at 10 days post-infection (dpi), with a booster injection of 25 μg at 12 dpi. Five mice from each group were sacrificed at 14 dpi for pathological examination and RNA extraction. The infiltration of eosinophils and severity of eosinophilic meningitis were reduced in 12D5 mAb-treated mice compared with the infected mice without 12D5 treatment. The levels of eotaxin mRNA expression in spleen significantly increased and the expression of the Th2-type cytokine IL-5 significantly decreased. However, the expression of IL-4 was not changed. 12D5 mAb can observably enhance the survival rate of infected mice and reduce symptoms of angiostrongyliasis. A. cantonensis infection is a major cause of eosinophilic meningoencephalitis. The results of this study could be helpful for the development of treatment of human angiostrongylosis.     

Inducible knockout of GRP78/BiP in the hematopoietic system suppresses Pten-null leukemogenesis and AKT oncogenic signaling

Traditionally, GRP78 is regarded as protective against hypoxia and nutrient starvation prevalent in the microenvironment of solid tumors; thus, its role in the development of hematologic malignancies remains to be determined. To directly elucidate the requirement of GRP78 in leukemogenesis, we created a biallelic conditional knockout mouse model of GRP78 and PTEN in the hematopoietic system. Strikingly, heterozygous knockdown of GRP78 in PTEN null mice is sufficient to restore the hematopoietic stem cell population back to the normal percentage and suppress leukemic blast cell expansion. AKT/mTOR activation in PTEN null BM cells is potently inhibited by Grp78 heterozygosity, corresponding with suppression of the PI3K/AKT pathway by GRP78 knockdown in leukemia cell lines. This is the first demonstration that GRP78 is a critical effector of leukemia progression, at least in part through regulation of oncogenic PI3K/AKT signaling. In agreement with PI3K/AKT as an effector for cytosine arabinoside resistance in acute myeloid leukemia, overexpression of GRP78 renders human leukemic cells more resistant to cytosine arabinoside-induced apoptosis, whereas knockdown of GRP78 sensitizes them. These, coupled with the emerging association of elevated GRP78 expression in leukemic blasts of adult patients and early relapse in childhood leukemia, suggest that GRP78 is a novel therapeutic target for leukemia.     

应用多点刺激法运动单位数目估计评定平山病病情

目的 探讨多点刺激法运动单位数目估计( MUNE)在平山病病情判定中的意义.方法 采用病例对照研究,记录35例健康人和69例平山病患者拇短展肌和小指展肌MUNE数值.结果 (1)平山病组左侧拇短展肌MUNE为145.66±126.10,左侧小指展肌MUNE为102.20±112.67,右侧拇短展肌MUNE为149.72±117.80,右侧小指展肌MUNE为64.23±69.27,较对照组显著降低(P＜0.01).(2)在临床尚未出现明显症状的肌肉也可见到MUNE明显下降,尤其在症状不显著侧(P＜0.05).结论 多点刺激法MUNE检测可客观监测疾病自然过程,早期了解病情及定量评价肌肉的失神经支配情况.     

Simultaneous modulation of COX-2, p300, Akt, and Apaf-1 signaling by melatonin to inhibit proliferation and induce apoptosis in breast cancer cells

Melatonin exhibits anti-inflammatory and anticancer effects and could be a chemopreventive and chemotherapeutic agent against cancers, but the precise mechanisms involved remain largely unresolved. In this study, we evaluated the mechanism of action of melatonin in human MDA-MB-361 breast cancer cells. Melatonin at pharmacological concentrations (10(-3) m) significantly suppressed cell proliferation and induced apoptosis in a dose-dependent manner. The observed suppression of proliferation was accompanied by the melatonin-mediated inhibition of COX-2, p300, and NF-κB signaling. Melatonin significantly inhibited COX-2 expression and prostaglandin E(2) (PGE2) production, abrogated p300 histone acetyltransferase activity and p300-mediated NF-κB acetylation, thereby blocking NF-κB binding and p300 recruitment to COX-2 promoter. Pretreatment with a COX-2- or p300-selective inhibitor abrogated the melatonin-induced inhibition of cell proliferation, whereas PGE2 treatment or COX-2 transfection reversed the inhibition by melatonin. Moreover, melatonin markedly inhibited phosphorylation of PI3K, Akt, PRAS40, and GSK-3 proteins, thereby inactivating the PI3K/Akt signaling pathway. Pretreatment with a PI3K- or an Akt-selective inhibitor or an Akt-specific siRNA blocked the melatonin-mediated inhibition of cell proliferation. Conversely, gene delivery of a constitutively active Akt effectively reversed the inhibition by melatonin. Furthermore, melatonin induced Apaf-1 expression, triggered cytochrome C release, and stimulated caspase-3 and caspase-9 activities and cleavage, leading to an activation of the Apaf-1-dependent apoptotic pathway. Pretreatment with an Apaf-1-specific siRNA effectively attenuated the melatonin-induced apoptosis. These results therefore indicate that melatonin inhibits cell proliferation and induces apoptosis in MDA-MB-361 breast cancer cells in vitro by simultaneously suppressing the COX-2/PGE2, p300/NF-κB, and PI3K/Akt/signaling and activating the Apaf-1/caspase-dependent apoptotic pathway.