开展口腔循证医学教育的必要性和可行性探讨

循证医学自1992年提出以来,其理念已经渗透到医学的各个领域,在规范和解决临床问题方面发挥着越来越重要的作用.但在13腔医学领域,循证医学的开展与普及情况尚不理想.在此从临床决策和临床科研两个方面,论述了开展13腔循证医学教育的必要性,并提出了口腔循证医学的教学内容、方法和考核手段.

Abstract：

The concept and methods of evidence-based medicine(EBM)has been evolved to impact almost all fields of health care and policy since it first appeared in 1992.but in the field of dentistry or stomatology,many problems remain to be solved in carrying out EBM.The necessity and feasibility of implementing evidence-based dentistry education in China were discussed in this paper for chnical evidence-based decision making and clinical research.The contenk teaching approach and accreditation tools for EBM in dental education were also proposed.     

解读慢性阻塞性肺疾病的现代病理生理学

编者按 Calverley博士是英国Liverpool大学呼吸医学教授,Liverpool大学Aintree医院的荣誉顾问,主要研究领域为慢性阻塞性肺疾病、睡眠与呼吸疾病的病理生理和治疗,为国际著名临床研究ISOLDE(Inhaled Steroids in Obstructive Lung Disease)和TRISTAN(Trial of Inhaled Steroids and Long-acting β2-agonists)的主要研究者.     

确定多指标医学参考值范围的统计方法

第十讲 多指标LMS法 多指标LMS法（LMS method of multiple indicatrixes）是针对18岁以前儿童生长发育参考值范围制定,对于多指标探讨应用多指标偏度系数（L）·中位数（M）·变异系数（S（coefficientofskewness,median,coefficient of variation in multiple indicatrixes）.偏度系数·中位数·变异系数法（coefficient of skewness,median,coefficient of variation.LMS）由TJ.Cole教授于1988年提出.1995年,Cole和Free—mall将其成功运用于拟合儿童身高、体重和体质指的生长曲线,使其成为评价儿童青少年生长发育的一种重要统计学方法.但TJ.Cole教授提出的是单指标LMS法,如用于制定单指标BMI参考值范围.     

循证医学在医学检验教学中的应用

循证医学本是一种新的临床医学模式,其理念和方法已经扩展到整个医学教育领域.七年制临床医学专业(医学检验方向)是为培养高层次医学检验医师而设立的新专业方向,在医学检验中引入循证医学理念具有重要意义.本文对循证医学原则在提高学生临床检验技能、培养学生科研创新能力、教会学生终身主动学习以及提高医学检验在临床实践中的地位等方面的应用进行了初步探讨.

Abstract：

Evidence-based medicine(EBM) is a new model of clinical medicine and its concepts and methods are extend to the field of medical education. Seven-year laboratory medicine program is a new professional, which is to train high-level laboratory examination physician. EBM is of great significance in laboratory medicial education. This article reviewed the principles of EMB in improving the students clinical examination skills, the students innovation ability, the students life-long learning habits and improving the status of laboratory medicine in clinical practice.     

Increased Expression and Altered Subcellular Distribution of Cathepsin B in Microglia Induces Cognitive Impairment through Oxidative Stress and Inflammatory Response in Mice

Objective：During normal aging，innate immunity progresses to a chronic state. However，how oxidative stress and chronic neuroinflammation arise during aging remain unclear. In this study，we intended to demonstrate the novel function of Cathepsin B （CatB） in the age related oxidative stress and chronic neuroinfl ammation. Methods：①2 month-old and 20 month-old wild-type and CatB-/- mice were used for learning and memory tests by step through passive avoidance tests. The cumulative potentiation of the fi eld excitatory postsynaptic potential（ fEPSP） slope and dendritic spine density were also examined. ②Infl ammation were examined by immunoblotting of interleukin-1β（ IL-1β），tumor necrosis factor-α（ TNF-α） and inducible nitric oxide synthase（ iNOS），and oxidative stress were examined by checking the level of 8-oxo-7，8-dihydro-2’-deoxyguanosine （8-oxo-dG） and 4-hydroxynonenal（ 4-HNE） in the hippocampal lysate of 2 month-old and 20 month-old wild-type and CatB-/- mice. ③Intra-lateral ventricle transplantation of CatB over-expressed microglia in middleaged mice，learning and memory were examined by Y-maze and novel objective tests. Results：①The retention latencies of both aged groups were significantly longer than those in the acquisition trial. The retention latency of four consecutive trials was signifi cantly longer in aged CatB-/- mice than in aged wild-type mice. Furthermore，the mean relative fEPSP slope measured at 30 min after stimulationwith 25，50 and 100 Hz in the aged CatB-/- mice was significantly larger than that in the aged wildtype mice. The mean dendritic spine density of CA1 neurons in the aged CatB-/- mice was signifi cantly
larger than that in the aged wild-type mice. ②The mean levels of CatB，iNOS，IL-1β and TNF-α in the hippocampus were signifi cantly higher in aged wild-type mice than in younger animals. Furthermore， their mean levels in the hippocampus of aged CatB-/- mice were significantly lower than those in aged wild-type mice. The mean amounts of these oxidative markers were significantly larger in the hippocampus of aged wild-type mice than in younger animals. The mean relative amount of 8-oxodG and 4-HNE was significantly lower in aged CatB-/- mice than in aged wild-type mice. ③Double immunohistochemical staining was conducted to identify the possible cellular origin of oxidative stress. In the hippocampus of aged wild-type mice，the immunoreactivities of both 8-oxo-dG and 4-HNE were found exclusively in microglia with activated morphology，but not in astrocytes or neurons. ④Intralateral ventricle transplantation of CatB over-expressed microglia signifi cantly impaired the learning and memory in the middle-aged mice. Conclusion：CatB plays a critical role in the mitochondriaderived ROS generation and infl ammatory response，resulting in impairment of learning and memory during normal aging.     

语义相反的“in”和“out of”短语

介词in和out of与名词搭配构成的短语,其语义特征经常是含有对应的相反语义。其表现形式可以归纳四种结构类型,同分述如下。 1 in/out of+n. 1.1 in danger在危险中:out of danger脱险 Your life has been in danger for my sake, dear friend. 好朋友,你曾为我冒过生命危险。     

A Novel Mechanism Underlying the Protective Effect of PDE4 Inhibitor Against Cognitive Impairment： Inhibiting Neuroinflammation through Inducing Autophagy in Microglial Cells

Background：Inhibition of phosphodiesterase 4 （PDE4） improves the learning and memory abilities in Alzheimer’s disease animal models. The cognition-enhancing effects of PDE4 inhibition involve reduced inflammatory responses in the brain. However，the underlying mechanisms are ill-understood. cAMP induces autophagy，and defi ciency of autophagy leads to elevated inflammatory factors. In the present study，we aimed to investigate the contribution of autophagy to the anti-inflammatory effect of PDE4 inhibitor ROF. Methods：Acidic vesicles were traced by Lysotracker（ LYT） red and acridine orange（ AO） staining. Autophagosomes in BV-2 cells were observed by immunofluorescence staining of microtubule-associated protein 1 light chain 3 （LC3）. Aβ25-35 or lipopolysaccharide （LPS） with ATP were used to activate microglial cells and infl ammasome. Cytokine levels were measured by ELISA method. The levels of pro-infl ammatory factors and essential proteins involved in the formation of autophagosome were detected by Western blotting. Results：ROF increased the level of LC3-II，while the level of p62 was decreased. Enhanced fl uorescent signals were observed in BV-2 cells treated with ROF by AO and LYT red staining. In addition，immunofl uorescence indicated a significant increase in punctate LC3. Both LPS plus ATP and Aβ25-35 enhanced the conversion ofpro-caspase-1 to cleaved-caspase-1 and increased the production of mature IL-1β. Interestingly，these effects were blocked by the treatment of ROF. Moreover，ROF decreased the apoptosis of neuronal N2a cells in conditioned media from BV-2 microglia. These effects were reversed by inhibition of microglial autophagy. Treatment with ROF also showed enhanced autophagy in mcie treated with LPS.Conclusions：PDE4 inhibitor ROF inhibits infl ammasome activities and reduces the release of IL-1β by inducing autophagy.     

The Critical Role of IL-10 in the Anti-neuroinflammatory and Anti-oxidative Effects of Rheum Tanguticum on Activated Microglia

Objective：Rheum tanguticum Maxim. ex Balf.（ Rt），a traditional Tibetan medicine，is known to exert various bioactivities，including anti-inflammatory and anti-oxidative activities. The present study was conducted to investigate anti-infl ammatory and anti-oxidative effects of Rt on activated microglia. Methods：①MG6 microglial cell line，primary microglia and mice brain slices culture were stimulated by chromogranin A（ CGA），an endogenous microglia activator，to induce proinfl ammation and oxidation. The anti-infl ammatory and anti-oxidative effects of Rt were examined by q-PCR，western blotting and ELISA by checking infl ammatory and oxidative molecules，including IL-1β，tumor necrosis factor-α，IL-10 and nitric oxide. ②Investigation of the involvement of IL-10 in the anti-infl ammatory effects of Rt on infl ammatory responses of microglia by using neutralizing antibodies against IL-10. Pro-infl ammatory molecules expression were checked by q-PCR.③Examination of the effects of major components of Rt（ aloe-emodin，（+）-cathechin，piceatannol chrisophanol，physcion，β-sitosterol and emodin） on the IL-10 mRNA expression in MG6 cells. Results：①The mean mRNA expression levels of TNF-α，IL-1β and iNOS were signifi cantly increased in MG6 cells at 24 h after stimulation with CGA. Rt signifi cantly suppressed the mean mRNA expression levels of TNF-α，IL-1β and iNOS in GGA-stimulated MG6 cells. Furthermore，the production of IL-1β and NO metabolites in the culture medium of MG6 cells were assessed by using ELISA and NO2-/NO3- assay，respectively. The mean levels of IL-1β and NO2-/NO3- signifi cantly increased in the culture medium of MG6 cells at 24 h after treatment with CGA. Rt also signifi cantly decreased the mean levels of IL-1β and NO2-/NO3- in the culture medium of MG6 cells. The mean protein level of IL-1β signifi cantly increased in the organotypic hippocampal slice cultures at 48 h after stimulation with CGA（ 10 nmol·L-1）. Rt signifi cantly suppressed the mean protein level of IL-1β in CGA-stimulated organotypic hippocampal slice cultures ②The neutralization of IL-10 restored the mean mRNA expression of TNF-α and IL-1β in CGA-stimulatedMG6 cells in the presence of Rt. ③Among the major components of Rt，three components namely， aloe-emodin （10 μmol·L-1），（+）-cathechin （30 μmol·L-1） and piceatannol （100 μmol·L-1），were found to signifi cantly increase the mRNA expression of IL-10 in MG6 cells at 24 h after treatment. In contrast， chrisophanol，physcion，β-sitosterol or emodin at concentrations up to 100 μmol·L-1 had no effect on the mRNA expression of IL-10 in MG6 cells. Conclusion：Rt suppressed the production of pro-infl ammatory and oxidative mediators，including IL-1β，TNF-α and NO，by cultured activated microglia through the production of IL-10. Two components of Rt，aloe-emodin and （+）-catechin，induced the secretion of IL- 10 from cultured microglia. Therefore，aloe-emodin and （+）-catechin are deemed responsible for the antineuroinfl ammatory and anti-oxidative effects of Rt through the secretion of IL-10 from microglia.     

Gender differences in pulmonary inflammation following systemic cadmium administration in rats

Objective To examine the presence of gender differences in pulmonary inflammation evoked by acute systemic cadmium administration in rats. Methods Presence of basic indicators of lung inflammation （inflammatory cytokine lung content, leukocyte infiltration and activity of cells recovered from lungs by enzyme digestion） was analyzed and compared in animals of the two sexes. Results Intraperitoneal administration of cadmium （1.0 mg/kg） resulted in higher cadmium content in lungs of female rats. Higher tumor necrosis factor （TNF） content was noted in lung homogenates of male rats, while interleukin-6 （IL-6） content was slightly, but signifaicantly greater in lungs of female rats. Increased leukocyte infiltration was observed in lungs of male rats, mainly due to neutrophils. Increased responsiveness to phorbol myristate acetate （PMA） stimulation was noted in cells recovered from lungs of male rats. Rise in intracellular content of myeloperoxidase （MPO） was noted in lung cells from cadmium-treated rats of both sexes, but higher in cells from male rats. Conclusion Presented data documented a more intense pulmonary inflammatory response to systemic cadmium administration in males, with higher IL-6 levels in lungs of female individuals. These sex differences in proinflamatory activity of cadmium in lungs should be taken into consideration in studying the remote toxicity of this heavy metal.     

Expression of phosphorylated-STAT3 and osteopontin and their correlation in melanoma

The expressions of p-STAT3 and osteopontin in 22 cases of normal nevi and 43 cases of malignant melanoma were immunohistochemically detected, and the correlation between p-STAT3 and osteopontin in malignant melanoma and the correlations of p-STAT3 （or osteopontin） with invasion, metastasis and thickness of malignant melanoma were examined. The results showed p-STAT3 was expressed in 2 of 22 cases of normal nevi and 30 of 43 cases of malignant melanoma, while osteopontin was expressed in 3 cases of normal nevi and 29 cases of malignant melanoma. The expressions of p-STAT3 and osteopontin in melanoma were significantly higher than that in benign nevi. There existed significant correlations between the expression of p-STAT3 and that of osteopontin in melanoma. Furthermore, the expression rates of p-STAT3 were significantly higher in invasive or metastatic melanomas than that their non-invasive or non-metastatic counterparts, and the expression rates of osteopontin were significantly higher in invasive melanomas than that in non-invasive ones. It is concluded that p-STAT3 and osteopontin may play important roles in the pathogenesis of malignant melanoma.     

PROMINENT PERSONNEL——LEI Yan （雷燕）：An Expert in Studying Cardiovascular Diseases with Integrated Medicine

Professor LEI Yan, Ph. D., female, was born in October 1960. After being graduated from Henan College of Traditional Chinese Medicine （ TOM ） in 1983, she worked as a resident physician in the TOM Hospital of Xinyang city, Henan province. She was enrolled in the master＇ s program of internal medicine of integrative traditional Chinese and Western medicine in Fujian College of TOM in 1988, and after finished her study in 1991, she was employed as a chief physician in Fujian Provincial Institute of Cardiovascular Diseases for two years. In 1993 she studied under the indoctrination of Prof. CHEN Ke-ji, majoring in cardiovascular diseases in the China Academy of Chinese Medical Sciences （CACMS） and got the doctoral degree in July 1996. In 1998, she finished the post-doctorate research on the prevention and treatment of senile dementia in Beijing University of Chinese Medicine. Since then, she took charge in managerial work as the assistant director of department of cardiovascular diseases of Xiyuan Hospital of CACMS and the director of department of scientific research supervisal in CACMS, meanwhile, as a Prof. of Medi- cine, the tutor of doctoral students on integrated traditional Chinese and Western medicine （TCM-WM） of CACMS.     

KAE Alleviates LPS-induced Neuroinflammation in the Striatum of Mice via Down-regulating TLR4/ MyD88 Signaling Pathway

Objective：Kaempferol（ KAE） is a natural fl avonoid with many biological activities including anti-oxidation and anti-inflammation. Nevertheless，the relevant mechanism of its antineuroinfl ammation remains unclear. The present study was to investigate the mechanism of KAE against LPS-induced neuroinfl ammation in the striatum of mice. Methods：Lipopolysaccharide （LPS），a lipid polysaccharide，can be used to establish animal inflammation model. Adult male BALB/c mice were treated with KAE 20 mg·kg-1 and 50 mg·kg-1 for 7 days. On the 7th day，the mice were treated with LPS 5 mg·kg-1 for 6 h. The levels of IL-1β，IL-6，TNF-α，MCP-1 and ICAM-1 in the striatum were determined by ELISA. The protein expression of TLR4，MyD88，HMGB1 and P2X7 in the striatum were detected by Western blotting. Results：KAE significantly decreased cytokines release including IL-1β，IL-6，TNF-α，MCP-1 and ICAM-1 in the striatum of mice induced by LPS. In addition，KAE also inhibited the infl ammatory proteins expression，such as TLR4，MyD88，HMGB1 and P2X7，in the striatum of mice induced by LPS. Conclusion：KAE alleviates LPS-induced neuroinfl ammation in the striatum of mice via inhibiting TLR4/MyD88 signaling pathway.     

Gender Differences in Acute Cadmium-Induced Systemic Inflammation in Rats

Objective To examine the presence of gender differences in pro-inflammatory potential of cadmium in rats by comparing systemic inflammatory response to acute cadmium intoxication in animals of the two sexes. Methods Basic aspects of this response were evaluated, including plasma levels of inflammatory cytokines tumor necrosis factor （TNF） and interleukin-6 （IL-6） and of major rat acute phase protein alpha 2-macroglobulin （alpba2-M）, as soluble indicators of inflammation, and the number and activity of peripheral blood leukocytes, as cellular indicators of inflammation. Results Differential increases of IL-6 and alpha 2-M （higher in males than in females） in peripheral blood cell counts and types （leukocytosis and shift in the ratio of granulocytes to lymphocytes more pronounced in males vs females） and in levels of neutrophil priming （higher in males vs females） were noted. Conclusion The data document a more intense inflammatory response to cadmium administration in males. The sex differences in inflammatory effects of cadmium might be taken into consideration in studying the toxicity of this heavy metal.     

浙江中医药大学童培建教授早期干预股骨头坏死新疗法在骨研究顶级杂志在线发表

浙江中医药大学骨伤研究所（浙江省骨伤研究所）副所长、浙江中医药大学附属第一医院骨伤科主任童培建教授团队于2014年10月27日在骨研究领域国际顶级杂志Journal of Boneand Mineral Research（《骨与矿物质研究杂志》，2013年IF：6．589）在线发表研究论文“Combination Treatment of Biomechanical Support and Targeted Intra-arterial Infusion of Peripheral Blood Stem Cells mobilized by granulocyte-colony stimulating factor for the Osteonecrosis of the Femoral Head： a randomised controlled clinical trial”（J Bone Miner Res. 2014 Oct 2？. DOI： 10. 1002/jbmr. 2390.）。     

Fuzheng Huayu Capsule (扶正化瘀胶囊) in the treatment of liver fibrosis: Clinical evidence and mechanism of action

Liver fibrosis represents the wound healing response to liver injury from a wide variety of etiologies.Remarkable progresses have been shown in the field of liver fibrosis in a range of areas in the past years.In particular,the reversibility of liver fibrosis has been well documented in both patients and animal models.Great progresses have been made in the treatment of liver fibrosis with Chinese medicine.This review summarizes the effects of Fuzheng Huayu Capsule(扶正化瘀胶囊,FZHYC) in treating liver fibrosis and inflammation induced by chronic hepatitis B in clinical trials and the mechanism of action of FZHYC in reversing liver fibrosis in vivo and in vitro experiments.     

非小细胞肺癌组织中Survivin与Fas/FasL的表达及其临床意义

目的 检测非小细胞肺癌(NSCLC)组织中Survivin、Fas/FasL的表达.方法 采用免疫组织化学法检测16例正常肺组织、48例肺鳞癌组织、38例肺腺癌组织中Survivin、Fas/FasL的表达.结果 正常肺组织中Survivin的阳性表达率为0,而在肺鳞癌和肺腺癌组织中Survivin的阳性表达率分别为79.17%和70.05%,与正常肺组织相比二者差异均有统计学意义(P<0.01);正常肺组织中Fas的阳性表达率为81.25%,与肺鳞癌(41.67%)和肺腺癌(43.37%)相比,差异均有统计学意义(P<0.05);Fas的表达与性别、组织学类型、TNM分期及有无淋巴结转移均无相关性.正常肺组织中FasL的阳性表达率为18.75%,低于肺鳞癌(72.92%)和肺腺癌(68.42%),P<0.05.NSCLC组织中FasL的表达与性别及组织学类型无关,与TNM分期和淋巴结转移有关.结论 Survivin基因异常表达而引起的细胞凋亡抑制在NSCLC的发生中起一定的作用,其过度表达提示NSCLC预后不良;NSCLC Fas低表达在其发病中可能有一定的作用;Fas/FasL可能参与了NSCLC凋亡的调节,在NSCLC逃逸机体免疫监控方面起重要作用,因此检测FasL的表达可能为临床判断肺癌淋巴结转移提供依据. Abstract： Objective To detect the expression of Survivin, Fas/FasL in non-small cell lung cancer(NSCLC) tissue. Methods We used immunohistochemistry to detect the expression of Survivin, Fas/FasL in 16 cases of normal lung, 48 cases of squamous carcinoma of lung tissue, 38 cases of adenocarcinoma of lung tissue. Results The positive rate of Survivin in normal lung tissue, squamous carcinoma and adenocarcinoma of lung were 0, 79.17% and 70.05% respectively, and there was significant difference between the normal and the two NSCLC groups(P<0.01). The positive rate of Fas in normal lung tissue(81.25%) was significantly higher than that in squamous carcinoma of lung(41.76%) and adenocarcinoma of lung(43.37%),P<0.05. The positive of FasL in normal lung tissue(18.75%) was significantly lower than that in SqCa(72.92%) and adenocarcinoma of lung(68.42%)(P<0.05). No relation was found between the expression of FasL and clinicopathologic factors including sex, histoclassification. And there was a relation between lymphnode metastasis and TNM stage of NSCLC. Conclusions Apoptosis inhibitition caused by abnormal survivin expression may participate in the onset and progression of NSCLC. The over-expression survivin suggests the bad prognosis in NSCLC. The expression of Fas protein in NSCLC was low, and might play a role in carcinogenesis of lung carcinoma. The expression of Fas/FasL in NSCLC may play an important role in the escape of tumor cells from immune function. The expression of FasL might be used as an objective indicator of metastasis potency of local lymph node.     

10 cases of meningioma in skull base clinical report treated by microsurgery

［Abstract］Objective　To summary the experience of microsurgery of meningioma in skull base treatment. Methods　To study the clinical data of 10 cases patients of meningioma in skull base who were subjected to microsurgery by using retrospective analysis. Among the 10 patients,there were 3 cases of meningioma of the olfactory groove. There were 2 cases of sphenoid ridge meningioma,meningioma in the middle cranial fossa, meningioma in the cerebellopontine angle respectively．There was 1 case of meningioma of velarium in temporal lobe. Results　In 7 cases, the meningioma was completely removed. And in another 3 cases, the meningioma got subtotal resection. During and after the operation, there were no severe complications observed or death occurrence in all the 10 cases of meningioma patients. Two months post of operation,all patients got a significant amelioration in their symptoms. A total of 9 cases were followed up. There was 1 case of IIa type meningioma recurred. Conclusion:     

Methylation of Gene CHFR Promoter in Acute Leukemia Cells

In order to explore whether gene CHFR was inactivated by methylation in leukemia cells, the expression of CHFR was examined before and after treatment with demethylation agent in Molt-4, Jurkat and U937 leukemia cell lines by means of RT-PCR， The methylation of promoter in Moh-4, Jurkat and U937 cells as well as 41 acute leukemia patients was analyzed by MS-PCR. The results showed that methylation of CHFR promoter was inactivated and could be reversed by treatment with a demethylating agent in Molt 4, Jurkat and U937. CHFR promoter methylation was detected in 39 % of acute leukemia patients. There was no difference in incidence of CHFR promoter methylation between acute myeloeytie leukemia and acute lymphocytic leukemia. In conclusion, CHFR is frequently inactivated in acute leukemia and is a good candidate for the leukemia supper gene. By affecting mitotic checkpoint function, CHFR inactivation likely plays a key role in tumorigenesis in acute leukemia. Moreover, the methylation of gene CHFR appears to be a good index with which to predict the sensitivity of acute leukemia to microtubule inhibitors.