成人盆底痉挛综合征型便秘的分型及其病理生理机制

目的:探讨成人盆底痉挛综合征型便秘的分型及其病理生理机制,以及生物反馈治疗该型便秘的原理.方法:使用基础电路电压为1.53μV的Medtronic公司生产的生物反馈训练仪对18例盆底痉挛综合征型便秘的成人患者首先进行约20min放松练习,肛门塞电极记录到外括约肌的静息电位值,然后患者完成模拟排便动作,获得模拟排便及放松两种状态下外括约肌电位的两组数值,并进行统计学比较.结果:根据肛门外括约肌的静息电位以及模拟排便外括约肌的电位变化,成人盆底痉挛综合征型便秘表现为三种病理分型,即Ⅰ型:高静息电位+矛盾运动(占44.44%),Ⅱ型:高静息电位(占33.33%),Ⅲ型:矛盾运动(占22.22%),其中外括约肌的高静息电位占本组便秘患者的77.77%.各病理分型外括约肌静息电位之间两两比较均具有显著性差异(P=0.001).结论:外括约肌的高静息电位以及在此基础上并发的外括约肌矛盾运动构成了盆底痉挛综合征型便秘的病理生理机制,生物反馈训练能够有效降低外括约肌的静息电位并消除可能出现的外括约肌矛盾运动.

犬脑枪弹伤模型建立及相关生理、病理指标观察

目的 建立犬脑枪弹伤致伤模型 ,检验该模型用于颅脑枪弹伤进一步研究的可行性 .方法 杂种犬 14只 ,随机分成脑贯通伤 (PCI)组 (n =7)和脑切线伤 (TBI)组 (n =7) ,采用德国小口径步枪子弹按上述分组要求致伤 .测定弹丸致伤参数 ,观察实验犬伤后相关生理与病理指标改变 .结果 TBI组和PCI组的弹丸撞击速度与撞击能量基本一致 ;TBI组的组织对弹丸吸收能量较大 (P <0 0 5 ) ,且实验犬伤后存活时间也较长(P =0 0 0 13) .两组犬均在伤后数分钟至 1h内出现明显的心率减慢、血压下降、颈动脉血流量减少、呼吸暂停或减慢、颅内压 (ICP)逐渐升高 .两组挫伤区病理表现为脑血管扩张、充血、血管周围环形出血、神经细胞轻度缺血、坏死及脑水肿 .结论 上述模型均具有弹道伤恒定、重复性好、伤后动物存活时间较长等特点 。

Vascular Calcification:Where is the Cure?

With the progress of aging,the incidence of vascular calcification(VC)gradually increases,which is correlated with cardiovascular events and all-cause death,aggravating global clinical burden.Over the past several decades,accumulating approaches targeting the underlying pathogenesis of VC have provided some possibilities for the treatment of VC.Unfortunately,none of the current interventions have achieved clinical effectiveness on reversing or curing VC.The purpose of this review is to make a summary of novel perspectives on the interventions of VC and provide reference for clinical decision-making.

河南省城市社区卫生服务利用现状

目的了解河南省城市社区慢性病监测网络中高血压、糖尿病患者对社区卫生服务的利用情况。方法对河南省城市社区慢性病监测试点的高血压、糖尿病患者进行面对面问卷调查。结果1/3以上的高血压、糖尿病管理患者将社区作为知识获取的第一途径;对社区卫生服务基本满意率为92.9%;6个月内到社区就诊率平均为64.6%;86.0%的高血压患者和54.1%糖尿病患者能做到1月内定期测量血压和检测血糖;60%的管理患者选择社区就诊;80.03%以上的管理患者接受了药物性治疗,有56.7%～82.3%的管理患者接受了非药物性治疗服务。结论要积极推广社区高血压、糖尿病综合防控适宜技术,加强患者规范管理,提升社区卫生服务能力,促进居民对社区卫生服务的利用。

肾阴虚证的现代研究进展

肾阴虚证是中医学的基本证型之一。时中医证的研究,基本方法是运用现代科技手段,通过动物实验与临床研究,探讨疾病发生后"证"与人体生理变化、病理、生化等客观指标的关系,尝试揭示证的实质。几十年来,不少学者从细胞、分子等水平上对肾阴虚证本质做了深入地研究,并已取得了一定的成果,某些方面已形成了共识。这不仅丰富和发展了传统的中医肾阴虚理论,而且为肾阴虚证的临床诊断、治疗、预后判断提供了更客观的、更全面的指导作用。本文从神经内分泌、免疫、微量元素、脂代谢、自由基、细胞因子与介质、基因等方面对肾阴虚证病理生理的客观化研究进展进行了详细地阐述。

脂蛋白相关磷脂酶A_2、同型半胱氨酸和D-二聚体与原发性高血压相关性分析

目的:探讨脂蛋白相关磷脂酶A_2(LP-PLA_2)、同型半胱氨酸(Hcy)和D-二聚体(DDime)与原发性高血压的相关性。方法:选择无其他任何危险因素的原发性高血压疾病患者75例(无危险因素疾病组)和伴有hs-CRP、体重指数、总胆固醇、甘油三酯、LDL-C、血糖等至少一项以上危险因素的原发性高血压疾病患者66例(危险因素疾病组)及原发性高血压合并症患者(包括合并脑梗死、脑出血、冠心病、颈动脉斑块等动脉粥样硬化性心脑血管疾病)43例(原发性高血压合并症组);另选择同期健康体检者114名作为正常对照组。应用酶联免疫吸附法测定四组血浆脂蛋白相关磷脂酶A_2、速率法测定四组同型半胱氨酸,采用透射比浊法测定四组D-二聚体水平,分析脂蛋白相关磷脂酶、同型半胱氨酸和D-二聚体与原发性高血压的相关性。结果:无危险因素疾病组、危险因素疾病组和原发性高血压合并症三组中LP-PLA_2、Hcy、D-Dime的血液浓度显著高于正常对照组(P<0.01),且逐渐升高(P<0.01或P<0.05);无危险因素疾病组、危险因素疾病组和原发性高血压合并症三组患者中Hcy、D-Dime和LP-PLA_2三者呈明显正相关性(r=0.854,P<0.05)。结论:在心血管疾病的发生、发展过程中既存在有多因素的相互协同作用,也有疾病促进炎症因子的释放而存在因果关系相互促进的叠加效应。

The selective 5-HTIA receptor antagonist WAY-100635 inhibits neuronal activity of the ventromedial prefrontal cortex in a rodent model of Parkinson's disease

Objective The ventral part of the medial prefrontal cortex（mPFC）plays an important role in initiation and control of voluntary movement,mood and cognition.However,after the degeneration of the nigrostriatal pathway,the neuronal activity of the ventral mPFC and the role of serotonin1A（5-hydroxytryptamine,5-HT1A）receptors in the firing of the neurons are still unknown.The present study is to investigate the change of neuronal activity in the ventral mPFC and the effect of systemic administration of the selective 5-HT1Areceptor antagonist WAY-100635 on the activity of the neurons in normal and 6-hydroxydopamine（6-OHDA）-lesioned rats.Methods Single unit responses were recorded extracellularly with glass microelectrodes from ventral mPFC neurons in normal rats and 6-OHDA unilaterally lesiond rats in vivo.Results 6-OHDA lesion of the substantia nigra pars compacta（SNc）significantly increased the firing rate with no change in the firing pattern of neurons of the ventral mPFC in rats.Systemic administration of WAY-100635（0.1 mg/kg,i.v.）did not change the mean firing rate and firing pattern of ventral mPFC neurons in normal rats.In contrast,WAY-100635 signifi- cantly decreased the mean firing rate of the neurons in rats with 6-OHDA lesion of the SNc.Conclusion These data suggest that the degeneration of the nigrostriatal pathway results in an increase of neuronal activity of ventral mPFC and dysfunction of 5-HT1Areceptor.

Expression of vascular endothelial growth factor and its prognostic significance in gastric carcinoma

AIMS To investigate the clinical significance of vas- cular endothelial growth factor (VEGF) expression in gastric carcinoma. METHODS The expression of VEGF in 128 gastric carcinomas was investigated by immunohistochemical staining with a polyclonal antibody against VEGF. Cor- relations between the expression of VEGF and various clinicopathologic factors and prognosis were studied. RESULTS The VEGF-rich expression rate was 64.1% in gastric carcinoma. VEGF-rich expression rate of patients with stage Ⅲ and stage Ⅳ disease was greater than that of patients with stage f disease (P <0.05). Significant differences of expression rate ex- isted with respect to growth pattern,serosal invasion and lymph node metastasis. The VEGF-rich rate was much higher in tumors with expanding growth pattern (71.8%) or serosal invasion (73.5%) than in those with infiltrative growth pattern (52.0%) or non-serosal invasion (53.3%) (P<0.025,respectively),and it was also significantly higher in patients with lymph node metastases (75.0%) than in those without such metastases (50.0%) (P<0.05). In addition,postop- erative survey of 86 patients who had been followed up for at least 5 years demonstrated that the 5-year sur- vival rate of patients with VEGF-rich tumors was signifi- cantly lower than that of patients with VEGF-poor tu- mors (P<0.05). CONCLUSIONS The expression of VEGF may be as- sociated with the invasion and metastasis and may also be a useful prognostic indicator of gastric carcinoma.

Application of Support Vector Machine to Predict 5-year Survival Status of Patients with Nasopharyngeal Carcinoma after Treatment

Objective： Support Vector Machine （SVM） is a machine-learning method, based on the principle of structural risk minimization, which performs well when applied to data outside the training set. In this paper, SVM was applied to predict 5-year survival status of patients with nasopharyngeal carcinoma （NPC） after treatment, we expect to find a new way for prognosis studies in cancer so as to assist right clinical decision for individual patient. Methods： Two modelling methods were used in the study; SVM network and a standard parametric logistic regression were used to model 5-year survival status. And the two methods were compared on a prospective set of patients not used in model construction via receiver operating characteristic （ROC） curve analysis. Results： The SVM1, trained with the 25 original input variables without screening, yielded a ROC area of 0.868, at sensitivity to mortality of 79.2% and the specificity of 94.5%. Similarly, the SVM2, trained with 9 input variables which were obtained by optimal input variable selection from the 25 original variables by logistic regression screening, yielded a ROC area of 0.874, at a sensitivity to mortality of 79.2% and the specificity of 95.6%, while the logistic regression yielded a ROC area of 0.751 at a sensitivity to mortality of 66.7% and gave a specificity of 83.5%. Conclusion： SVM found a strong pattern in the database predictive of 5-year survival status. The logistic regression produces somewhat similar, but better, results. These results show that the SVM models have the potential to predict individual patient＇s 5-year survival status after treatment, and to assist the clinicians for making a good clinical decision.

The Establishment and Characterization of a Continuous Cell Line of Mouse Cervical Carcinoma

OBJECTIVE To establish a murine uterine cervical cancer cell line and to define its biological characters. METHODS Transplanted tumor tissue was used for in vitro primary culture of U14 cervical carcinoma cells. After 20 passages, we examined its morphology, chromosomes, tumorigenicity and produced a growth curve. CK was detected by immunohistochemistry, the cell cycle determined by flow cytometry and the metastatic potential assessed in 615 and C57BL/c mice. We also transfected the cells with the pEGFP-N1 plasmid. RESULTS A newly established murine cell line was passaged 50 times over a period of 10 months. The cells grow as a partially suspended culture, and are immunohistochemically CK（＋）. The cell line is characterized by a hypotetraploid karyotype, a chromosomal number of 64-68 and a doubling time of 21.8 h. Exponential growth occurs by the third and forth day of culture. Cell cycle analysis showed G1 34%, G2 26%, and 40% in the S phase. The tumorigenicity was 100% upon implantation. No mycoplasma contamination was detected. A monoclonal continuous U14-GFP cell strain which was 100% GFP （＋） was also produced. CONCLUSION We successfully established a new murine cervical U14 carcinoma cell line and an U14-GFP monoclonal strain. These cell lines are ideal for combined in vivo and in vitro tumor research.

1例GnRH激动剂诱发的卵巢过度刺激报道(法)

We report a case of ovarian hyperstimulation induced by a GnRH agonist (Decapeptyl) in a patient aged of 23 years and having 3 years of primary infertility of male origin. Twelve days after agonist administration, several ovarian follicles, great-sized, and with a rate of elevated serum oestradiol have been noted. After triggering of the ovulation by 5000 IU of HCG, oocyte retrieval permitted the collection of 4 oocytes 3 of which were mature. Only one embryo with 4 cells has been transferred 48 hours after intracytoplasmic sperm injection fertilization (ICSI), but there was no pregnancy. Ovarian hyperstimulation induced by GnRH agonist is a rare event and only a few cases have been reported. The development of multiple follicles after the administration of an agonist is a paradoxal answer of the ovary to the pituitary desensitization without a clarified physto- pathology. The hypothesis of a direct action of the agonist on the ovary is likeliest. Triggering of ovulation by human chorionic gonadotrophin (HCG) has been achieved by certain authors. Fertilization of oocytes and transfers of embryos have succeeded in certain cases, but only one pregnancy has been reported that led to a living birth.

Pathophysiology of pulmonary complications of acute pancreatitis

Acute pancreatitis in its severe form is complicated by multiple organ system dysfunction, most importantly by pulmonary complications which include hypoxia, acute respiratory distress syndrome, atelectasis, and pleural effusion. The pathogenesis of some of the above complications is attributed to the production of noxious cytokines. Clinically significant is the early onset of pleural effusion, which heralds a poor outcome of acute pancreatitis. The role of circulating trypsin, phospholipase A2, platelet activating factor, release of free fatty acids, chemoattractants such as tumor necrsosis factor （TNF）- alpha, interleukin （IL）-1, IL-6, IL-8, fMet-leu-phe （a bacterial wall product）, nitric oxide, substance P, and macrophage inhlbitor factor is currently studied. The hope is that future management of acute pancreatitis with a better understanding of the pathogenesis of lung injury will be directed against the production of noxious cytokines.

Functional dyspepsia:Are psychosocial factors of relevance?

The pathogenesis of Functional Dyspepsia （FD） remains unclear, appears diverse and is thus inadequately understood. Akin to other functional gastrointestinal disorders, research has demonstrated an association between this common diagnosis and psychosocial factors and psychiatric morbidity. Conceptualising the relevance of these factors within the syndrome of FD requires application of the biopsychosocial model of disease. Using this paradigm, dysregulation of the reciprocal communication between the brain and the gut is central to symptom generation, interpretation and exacerbation. Appreciation and understanding of the neurobiological correlates of various psychological states is also relevant. The view that psychosocial factors exert their influence in FD predominantly through motivation of health care seeking also persists. This appears too one-dimensional an assertion in light of the evidence available supporting a more intdnsic aetiological link. Evolving understanding of pathogenic mechanisms and the heterogeneous nature of the syndrome will facilitate effective management. Co-morbid psychiatric illness warrants treatment with conventional therapies. Acknowledging the relevance of psychosocial variables in FD, the degree of which is subject to vadation, has implications for assessment and management. Available evidence suggests psychological therapies may benefit FD patients particularly those with chronic symptoms. The rationale for use of psychotropic medications in FD is apparent but the evidence base to support the use of antidepressant pharmacotherapy is to date limited.

Pathophysiology and prevention of postoperative peritoneal adhesions

Peritoneal adhesions represent an important clinical challenge in gastrointestinal surgery. Peritoneal adhesions are a consequence of peritoneal irritation by infection or surgical trauma, and may be considered as the pathological part of healing following any peritoneal injury, particularly due to abdominal surgery. The balance between fi brin deposition and degradation is critical in determining normal peritoneal healing or adhesion formation. Postoperative peritoneal adhesions are a major cause of morbidity resulting in multiple complications, many of which may manifest several years after the initial surgical procedure. In addition to acute small bowel obstruction, peritoneal adhesions may cause pelvic or abdominal pain, and infertility. In this paper, the authors reviewed the epidemiology, pathogenesis and various prevention strategies of adhesion formation, using Medline and PubMed search. Several preventive agents against postoperative peri-toneal adhesions have been investigated. Their role aims in activating fi brinolysis, hampering coagulation, diminishing the inflammatory response, inhibiting col-lagen synthesis or creating a barrier between adjacentwound surfaces. Their results are encouraging but most of them are contradictory and achieved mostly in animal model. Until additional fi ndings from future clinical researches, only a meticulous surgery can be recommended to reduce unnecessary morbidity and mortality rates from these untoward effects of surgery. In the current state of knowledge, pre-clinical or clini-cal studies are still necessary to evaluate the effective-ness of the several proposed prevention strategies of postoperative peritoneal adhesions.

Role of Kupffer cells in the pathogenesis of liver disease

Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by produdng harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. Moreover they may represent a significant source of chemoattractant molecules for cytotoxic CD8 and regulatory T cells. Their role in fibrosis is well established as they are one of the main sources of TGFβ1 production, which leads to the transformation of stellate cells into myofibroblasts. Whether all these variable functions in the liver are mediated by different Kupffer cell subpopulations remains to be evaluated. In this review we propose a model that demonstrates the role of Kupffer cells in the pathogenesis of liver disease.

Bile acids:Chemistry,physiology,and pathophysiology

The family of bile acids includes a group of molecular species of acidic steroids with very peculiar physical-chemical and biological characteristics.They are synthesized by the liver from cholesterol through several complementary pathways that are controlled by mechanisms involving finetuning by the levels of certain bile acid species.Although their best-known role is their participation in the digestion and absorption of fat,they also play an important role in several other physiological processes.Thus,genetic abnormalities accounting for alterations in their synthesis,biotransformation and/or transport may result in severe alterations,even leading to lethal situations for which the sole therapeutic option may be liver transplantation.Moreover,the increased levels of bile acids reached during cholestatic liver diseases are known to induce oxidative stress and apoptosis,resulting in damage to the liver parenchyma and,eventually,extrahepatic tissues.When this occurs during pregnancy,the outcome of gestation may be challenged.In contrast,the physical-chemical and biological properties of these compounds have been used as the bases for the development of drugs and as pharmaceutical tools for the delivery of active agents.

Estrogens and the pathophysiology of the biliary tree

The scientific framework concerning estrogen effects on different tissues has expanded enormously during the last decades, when estrogen receptor （ER） subtypes were identified. Estrogens are not only essential for the female reproductive system, but they also control fundamental functions in other tissues including the cardiovascular system, bone, brain and liver. Recently, estrogens have been shown to target the biliary tree, where they modulate the proliferative and secretory activities of cholangiocytes, the epithelial cells lining bile ducts. By acting on both estrogen receptors （ER-α） and （ER-β） subtypes, and by activating either genomic or non-genomic pathways, estrogens play a key role in the complex loop of growth factors and cytokines, which modulates the proliferative response of cholangiocytes to damage. Specifically, estrogens activate intracellular signalling cascades JERK1/2 （extracellular regulated kinases 1/2, PI3-kinase/AKT （phosphatidylinositol-3＇ kinase/AKT）] typical of growth factors such as insulin like growth factor （IGF1）, nerve growth factor （NGF） and vascular endothelial growth factor （VEGF）, thus potentiating their action. In addition, estrogens stimulate the secretion of different growth factors in proliferating cholangiocytes. This review specifically deals with the recent advances related to the role and mechanisms by which estrogens modulate cholangiocyte functions in normal and pathological conditions.

Novel mechanisms in functional dyspepsia

Functional dyspepsia （FD） is a highly prevalent but heterogeneous disorder in which multiple pathogenetic mechanisms are involved. Although there are many studies that have investigated various pathophysiologic mechanisms, the underlying casual pathways associated with FD remain obscure. The currently proposed pathophysiologic mechanisms associated with FD include genetic susceptibility, delayed as well as accelerated gastric emptying, visceral hypersensitivity to acid or mechanical distention, impaired gastric accommodation, abnormal fundic phasic contractions, abnormal antroduodenal motility, acute and chronic infections, and psychosocial comorbidity. A greater understanding of the abnormalities underlying FD may lead to improved management. The aim of this editorial is to provide a critical overview of current pathophysiologic concepts in functional dyspepsia.