疑似脓毒症诊断生物标志物研究进展

脓毒症(sepsis)是一种机体对感染反应失调导致的器官功能障碍综合征[1],其发病机制极为复杂,涉及炎症、免疫、凝血等系统。当病情进展至严重脓毒症或脓毒症性休克时,危重症患者的死亡风险明显升高[2]。因此,在脓毒症患者发病早期出现感染迹象或症状,但尚未表现出明显的全身性感染反应或多器官功能障碍时(即疑似脓毒症阶段),快速诊断预测脓毒症,并尽早给予有效干预,阻止脓毒症发生进展,是提高其生存率的关键[3]。由于脓毒症早期症状、体征无特异性,且缺乏有效诊断措施,疑似脓毒症阶段的评估难度较大[4]。生物标志物是机体病理状态下出现的一些异常分子结构和功能变化,可为各种脏器功能损害提供早期预警[5]。近年来,越来越多生物标志物已经被用于脓毒症的早期诊断,在预测脓毒症发病情况及改善其预后生存率方面发挥了重要作用[6]。本文对疑似脓毒症的生物标志物进行系统分析,以期为临床脓毒症的早期诊断提供思路。

中西医临床的差异比较与结合

一、中西医临床的差异比较 (一) 整体与局部中医最显著的特征集中表现为"整体观念",其核心认为人体是一个以五脏为中心,通过经络气血联系内外上下的有机整体,同时认为"人与天地相应",人与自然界也是息息相关不可分割的,

新技术与辨证论治

辨证论治是中医理、法、方、药在临床上的具体运用。是指导中医临床工作的理论原则和诊疗疾病的统一规范。它属于辩证思维的范畴,总体上是正确的,经过几千年临床实践证明,辨证论治是行之的效的。但在某些细节上还显得比较笼统,不够精细。在当代科学技术飞速发展的时期,新技术革命必然对辨证论治产生巨大影响,将使中医学对疾病的认识更加准确,深刻,对疾病的治疗也将会有更好的效果,从而把祖国医学推到一个崭新的阶段,这是历史发展的必然趋势。本文就新技术革命对辨证论治的影响谈些个人浅见。如有谬误,请同道斧正。一、新技术革命对辩证思维的影响中医学的辩证思维受古代自然哲学的影响。

罗哌卡因局部区域阻滞联合帕瑞昔布钠的超前多模式镇痛对腹腔镜手术患者的影响分析

腹腔镜手术由于其具有着手术创伤小、患者术后恢复快以及对机体内环境干扰轻等优势而被临床各科室广泛使用。

维生素D_3低剂量连续给药对大鼠肾脏超微结构的变化

观察超微结构的变化是揭示机体病理变化机制的重要手段之一,是研究细胞亚显微结构的有力手段。大剂量维生素D3可造成模型大鼠肾脏组织钙盐沉积,从而造成维生素D3中毒大鼠模型肾脏功能损伤[1],但对低剂量连续用药大鼠肾脏肾小球超微结构的变化研究很少[2],文献[3]报道对维生素D3造成大鼠高血钙中毒模型肾组织超微结构的变化,主要观察了对肾近、远曲小管的影响,笔者至今未见有对肾小球超微结构的变化的研究报道。

腹腔积液常用生化指标在基层医院的诊断价值

腹腔积液是机体病理改变的一种重要体症,在众多病因中,主要是肝硬化、恶性肿瘤、结核性腹膜炎[1],鉴别诊断这些病因,于临床治疗有重要指导作用。腹腔积液检查项目繁多,病理学检验可初步判断腹腔积液来源;细胞计数及形态学检查是确诊恶性腹腔积液的＂金标准＂;肿瘤标志物检测也可从侧面印证恶性腹腔积液;生化检查（糖类及其衍生物、蛋白质类、酶类、脂类及胆红素类等）,而腹腔积液中的常用生化指标（糖、总蛋白、白蛋白、

Relationship between Vascular Elasticity and Spontaneous Rupture of Hepatocellular Carcinoma

Objective Spontaneous rupture of hepatocellular carcinoma (HCC) is common in Asia and Africa with unclear mechanism. In our previous study, we found that the deposition of immune complex on vascular wall and vascular injury were related to the HCC rupture. In this study, the structure of elastin around the small artery was deeply investigated to confirm our previous study. Methods Immunohistochemical technique and transmission electron microscopy were used to study 23 specimens from ruptured HCC and 30 cases of nonruptured HCC. Results The layer of elastin around the vascular wall was significant thicker in patients with ruptured HCC than that in nonruptured HCC. The proliferation of elastin, abnormal distribution of neutrophil elastase and degradation of collagen fibril were predominantly present in the specimens from ruptured HCC. The phenomenon of electron—dense deposit in the elastic lamina that represented the deposition of immune complex, and the signs of infiltrated neutrophils from bloodstream into the vascular wall that caused the vascular injury, also can be found in ruptured HCC. Since the damaged vessels could become stiff and weak, which would more prone to be splitting and results in hemorrhage and the rupture of HCC, we postulated that the preexisting of immune complex deposition and vascular injury may be relate to the ruptured HCC. Conclusion The vascular injury caused by immune complex deposition might relate to ruptured HCC. Key words hepatocellular carcinoma - rupture - elastin - elastase

测定血清、尿溶菌酶对矽肺诊断的探讨

1966年 Allison 等报告:石英粉尘吸入肺后,破坏溶酶体,释放溶菌酶,导致肺部纤维化。根据这一理论,我们于1982年对大连玻璃厂的工人进行了血清、尿溶菌酶的测定,现将结果报告于下:

老年人膳食护理

随着医学科学的发达,人们生活水平的提高,我们可以通过各种方法达到延缓衰老,其中饮食调理最为重要。生物的寿命与遗传的影响有关,但环境及后天的因子也不可忽视,最引人注目的是饮食和营养。因此对老年人的膳食护理必须重视。祖国医学认为:“脾为后天之本”,对老年人无论是治病还是养生都应以调理脾胃入手。

Action and mechanism of Fas and Fas ligand in immune escape of gallbladder carcinoma

AIM: To study the role of Fas and Fas ligand (FasL) in biological behaviors of gallbladder carcinoma, and their correlated action and mechanism in tumor escape.METHODS: Streptavidin-biotin-peroxidase immunohistochemistry technique was used to study the expression of Fas and FasL protein in 26 gallbladder carcinoma tissues,18 gallbladder adenoma tissues, 3 gallbladder dysplasia tissues and 20 chronic cholecystitis tissues. Apoptosis of the infiltrating lymphocytes in these tissues was studied by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Expression of both proteins and apoptosis of the tumor infiltrating lymphocytes in cancer tissues of primary foci was compared with clinicopathological features of gallbladder carcinoma.RESULTS: The positive rates of Fas were not significantly different among carcinoma, adenoma, dysplasia and chronic cholecystitis. The positive rate of FasL in carcinoma was significantly higher than that in chronic cholecystitis (x2 = 4.89, P＜0.05). The apoptotic index (AI) in carcinoma was significantly higher than that in adenoma (t'= 4.19, P＜0.01) and chronic cholecystitis (t'= 8.06, P＜0.01). The AI was significantly lower in well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma than that in poorly-differentiated carcinoma (t'= 2.63, P＜0.05) and Nevin Ⅳ-Ⅴ carcinoma(t'= 3.33, P＜0.01). The confidence interval (CI) ofinfiltrating lymphocytes in adenoma, chronic cholecystitis, well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma wasvery significantly lower than that in carcinoma (t' = 6.99,P＜0.01), adenoma (t' = 3.66, P＜0.01), poorly-differentiated carcinoma (t' = 5.31, P＜0.01) and Nevin Ⅳ-Ⅴ carcinoma(t' = 3.76, P＜0.01), respectively. The CI of apoptosis of infiltrating lymphocytes in well-differentiated carcinoma was significantly lower than that in poorly-differentiated carcinoma (t = 2.52, P＜0.05), and was not significantly lower in Nevin Ⅰ-Ⅲ carcinoma than in Nevin Ⅳ-Ⅴ carcinoma (t = 1.42, P＞0.05). Apoptosis of infiltrating lymphocytes was not discovered in adenoma and chronic cholecystitis. CONCLUSION: FasL expressed in gallbladder carcinoma cells permits tumor cells to escape from immune surveillance of organism by inducing apoptosis in infiltrating lymphocytes of carcinoma tissues. Up-regulation of FasL expression plays an important role in invasive depth, histological classification and metastasis of gallbladder carcinoma.

High concentration of antimitochondrial antibodies predicts progressive primary biliary cirrhosis

AIM： To evaluate the serum concentration of antimitochondrial antibodies （AMAs） as a prognostic indicator of progressive primary biliary cirrhosis （pPBC）. METHODS： Serum concentrations of AMA subtypes （anti-M2, anti-M4, and anti-M9）, biochemical indices of liver function and Mayo risk factor （MRF） were determined in 30 women with diagnosed primary biliary cirrhosis （PBC） selected among 348 females with elevated alkaline phosphatase but without signs of hepatic decompensation. They were followed up for 5 years for possible development of hepatic decompensation. RESULTS： Anti-M2 concentration was significantly correlated with bilirubin and albumin levels as well as MRF, whereas anti-M4 was significantly correlated with albumin level, prothrombin time and MRF. During the 5-year follow-up, progressive PBC （pPBC） was diagnosed in 3 among 23 patients available for evaluation. These 3 patients were positive for both anti-M2 and anti-M4. Anti-M2 serum concentration exceeded 1 300 RU/mL in patients with pPBC and only in 1 among 20 non-progressive PBC persons （5%）. Anti-M4 serum concentration exceeded 400 RU/mL in 2 of the progressive patients and none in the non-progressive group. In contrast, anti-M9 serum concentration was below 100 RU/mL in all patients with pPBC, and higher than 100 RU/mL in 11 women （55%） among the non-progressive group. CONCLUSION： Females with elevated alkaline phosphatase and high anti-M2 and anti-M4 concentrations are at a high risk for developing pPBC. Quantitative AMA detection should be considered as a method for early diagnosis of pPBC. 2005 The WJG Press and Elsevier Inc. All rights reserved.

Overexpression of decoy receptor 3 in hepatocellular carcinoma and its association with resistance to Fas ligand-mediated apoptosis

AIM： To characterize the expression and genomic amplification of decoy receptor 3 （DcR3） in hepatocellular carcinoma （HCC） and to evaluate the role of DcR3 in apoptosis.METHODS： We examined 48 cases of HCC for DcR3 expression by RT-PCR and DcR3 gene amplification by quantitative genomic PCR. DcR3 protein was detected by immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick and labeling （TUNEL） was used to identify the apoptosis cells in tissues. Primary hepatoma cell culture and MTT test were used to evaluate the protection against FasL- and chemicalinduced apoptosis by DcR3 expression. RESULTS： DcR3 mRNA overexpression was detected in 60% HCC （29/48） patients. The occurrence of HCC was not associated with amplification of the gene. One sample base substitution was found in three sites as a sequence in Genbank. The expression of DcR3 in HCC was associated with the apoptotic index （0.067±0.04 vs 0.209±0.12, P〈0. 01）, size of mass, stage, and infiltration or metastasis （41.2% vs71.0%, 40% vs75%, 51.8% vs84.6%, P〈0. 05）. DcR3 expression could protect hepatoma cells against apoptosis induced by FasL, but not by chemicals. CONCLUSION： These data suggest that in addition to gene amplification there may be another mechanism underlying DcR3 overexpression. The effect of overexpression of DcR3 on the apoptosis of cancer cells may have direct therapeutic implications for the management of HCC.

Significance of endothelial dysfunction in the pathogenesis of early and delayed radiation enteropathy

This review summarizes the current state of knowledge regarding the role of endothelial dysfunction in the pathogenesis of early and delayed intestinal radiation toxicity and discusses various endothelial-oriented interventions aimed at reducing the risk of radiation enteropathy. Studies published in the biomedical literature during the past four decades and cited in PubMed, as well as clinical and laboratory data from our own research program are reviewed. The risk of injury to normal tissues limits the cancer cure rates that can be achieved with radiation therapy. During treatment of abdominal and pelvic tumors, the intestine is frequently a major close-limiting factor. Microvascular injury is a prominent feature of both early （inflammatory）, as well as delayed （fibroproliferative） radiation injuries in the intestine and in many other normal tissues. Evidence from our and other laboratories suggests that endothelial dysfunction, notably a deficiency of endothelial thrombomodulin, plays a key role in the pathogenesis of these radiation responses. Deficient levels of thrombomodulin cause loss of vascular thromboresistance, excessive activation of cellular thrombin receptors by thrombin, and insufficient activation of protein C, a plasma protein with anticoagulant, anti-inflammatory, and cytoprotective properties. These changes are presumed to be critically involved in many aspects of early intestinal radiation toxicity and may sustain the fibroproliferative processes that lead to delayed intestinal dysfunction, fibrosis, and clinical complications. In conclusion, injury of vascular endothelium is important in the pathogenesis of the intestinal radiation response. Endothelial-oriented interventions are appealing strategies to prevent or treat normal tissue toxicity associated with radiation treatment of cancer.

Etiopathogenesis of primary biliary cirrhosis

Primary biliary cirrhosis(PBC) is an autoimmune disease of the liver characterized by progressive bile duct destruction eventually leading to cirrhosis and liver failure.The serological hallmark of the disease is the presence of circulating antimitochondrial antibodies(AMA).These reflect the presence of autoreactive T and B cells to the culprit antigens,the E2 subunits of mitochondrial 2-oxo-acid dehydrogenase enzymes,chiefly pyruvate dehydrogenase(PDC-E2).The disease results from a combination of genetic and environmental risk factors.Genetic predisposition is indicated by the higher familial incidence of the disease particularly among siblings and the high concordance rate among monozygotic twins.Environmental triggering events appear crucial to disrupt a pre-existing unstable immune tolerance of genetic origin allowing,after a long latency,the emergence of clinical disease.Initiating mimetopes of the vulnerable epitope of the PDC-E2 autoantigen can be derived from microbes that utilize the PDC enzyme or,alternatively,environmental xenobiotics/chemical compounds that modify the structure of native proteins to make them immunogenic.A further alternative as a source of antigen is PDC-E2 derived from apoptotic cells.In the effector phase the biliary ductular cell,by reason of itsproclivity to express the antigen PDC-E2 in the course of apoptosis,undergoes a multilineage immune attack comprised of CD4+ and CD8+ T cells and antibody.In this article,we critically review the available evidence on etiopathogenesis of PBC and present interpretations of complex data,new developments and theories,and nominate directions for future research.

Involvement of pancreatic and bile ducts in autoimmune pancreatitis

AIM：To examine the involvement of the pancreatic and bile ducts in patients with autoimmune pancreatitis. METHODS： Clinical and cholangiopancreatographic findings of 28 patients with autoimmune pancreatitis were evaluated. For the purposes of this study, the pancreatic duct system was divided into three portions： the ventral pancreatic duct, the head portion of the dorsal pancreatic duct; and the body and tail of the dorsal pancreatic duct. RESULTS： Both the ventral and dorsal pancreatic ducts were involved in 24 patients, while in 4 patients only the dorsal pancreatic duct was involved. Marked stricture of the bile duct was detected in 20 patients and their initial symptom was obstructive jaundice. Six patients showed moderate stenosis to 30%-40% of the normal diameter, and the other two patients showed no stenosis of the bile duct. Although marked stricture of the bile duct was detected in 83% （20/24） of patients who showed narrowing of both the ventral and dorsal pancreatic ducts, it was not observed in the 4 patients who showed involvement of the dorsal pancreatic duct alone （P = 0.0034）. CONCLUSION： Both the ventral and dorsal pancreatic and bile ducts are involved in patients with autoimmune pancreatitis.

Toll-like receptors in inflammatory bowel disease-stepping into uncharted territory

Ulcerative colitis and Crohn's disease are chronic relapsing-remitting inflammatory processes of the intestinal tract. The etiology of these diseases is currently unknown. However, inflammation is hypothesized to result from inappropriate activation of mucosal immunity by luminal antigens in genetically susceptible individuals. Toll-like receptors (TLRs) are a family of transmembrane proteins that act as microbial pattern recognition receptors. They are crucial initiators of innate immune responses. The role of TLRs in the pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. In this review, we aim to analyze the available data connecting individual TLRs to intestinal inflammation and IBD.

Etiopathogenesis of primary sclerosing cholangitis

Primary sclerosing cholangitis(PSC) is a chronic cholestatic liver disease of unknown etiology but lymphocytic portal tract infiltration is suggestive of an immune-mediated basis for this disease.Associations with inflammatory bowel disease(IBD) especially ulcerative colitis(UC),and with particular autoimmune diseases,as well as the genetic associations further suggest PSC may be an immune-mediated disease.The immunogenetics of PSC have been the subject of active research and several HLA and non-HLA associated genes have been implicated in the development of the disease.Lymphocytes derived from the inflamed gut may enter the liver via the enterohepatic circulation to cause hepatic disease.PSC may be triggered in genetically susceptible individuals by infections or toxins entering the portal circulation through a permeable colon and hence evoking an abnormal immune response.

Disproportional exaggerated aspartate transaminase is a useful prognostic parameter in late leptospirosis

AIM: To evaluate the hepatic dysfunction in leptospirosis is usually mild and resolved eventually. However,sequential follow-up of liver biochemical data remained lacking..METHODS: The biochemistry data and clinical symptoms of 11 sporadic patients were collected and analyzed, focusing on the impacts of leptospirosis upon liver biochemistry tests.RESULTS: The results disclosed that of the 11 cases, 5 or 45% died. The liver biochemistry data in the beginning of the disease course were only mildly elevated.Nevertheless, late exaggerated aspartate transaminase (AST)elevations were noted in three cases who finally died when compared with the typical course. Besides, significant higher AST/alanine transaminase (ALT) ratios (AARs) of the peak levels for transaminase were also noted in the cases who eventually succumbed. The mean±SD of AARs for the survival group and dead group were 5.65±2.27 (n = 5)and 1.86±0.64 (n = 6) respectively (P= 0.006). The ratios of the cases who finally died were all more than 3.0.Conversely, the survival group's ratios were less than 3.0.CONCLUSION: Serial follow-up of transaminase might provide evidence to predict some rare evolutions in leptospirosis. If AST elevated progressively without a concomitant change of ALT, it might indicate an acute disease course with ensuing death. Additionally, AAR is another prognostic parameter for leptospirosis. Once the value was higher than 3.0, a grave prognosis is inevitable.

Investigation of stressful life events in patients with systemic sclerosis

Objective: To assess the occurrence of stressful life events in the year before the initiation of systemic sclerosis. Methods: A consecutive series of 40 patients with systemic sclerosis (mean age (56.3±11.9) years, mean disease duration (4.3±3.1) years; 32 females and 8 males), including 28 with diffuse cutaneous scleroderma and 12 with limited cutaneous scleroderma, were evaluated. A control group of 40 healthy subjects free of systemic sclerosis also was included. Socioeconomic status was inves- tigated and Paykel's interview for recent life events (a semi-structured research interview covering 64 life events) was conducted. Results: Patients with systemic sclerosis showed higher percentages of lower education (72.5%) and working class (82.5%), and reported more stressful life events (P<0.05), such as exits (P<0.05), undesirable events (P<0.01), and uncontrolled events (P<0.001), when compared with the control. More events that had an objective negative impact (P<0.001) were also reported in systemic sclerosis patients than in the control. These results are in accordance with a multifactorial model of pathogenesis in systemic sclerosis. Conclusion: We reported a strong relationship between stressful life events and the initiation of systemic sclerosis. Our findings are consistent with current understanding of the extensive links of behavioral responses to stress with neurophysiological and biochemical processes.

Usefulness of biopsying the major duodenal papilla to diagnose autoimmune pancreatitis:A prospective study using IgG4-immunostaining

AIM： TO examine the histological and immunohistochemical findings of biopsy specimens taken from the major duodenal papilla of autoimmune pancreatitis （AIP） patients. METHODS： The major duodenal papilla in the resected pancreas of 3 patients with AIP and of 5 control patients [pancreatic carcinoma （n = 3） and chronic alcoholic pancreatitis （17 = 2）] was immunostained using anti-CD4-T cell, CD8-T cell and IgG4 antibodies. Forceps biopsy specimens taken from the major duodenal papilla of 2 patients with AIP and 5 control patients with suspected papillitis were prospectively taken during duodenoscopy and immunohistochemically examined. RESULTS： Moderate or severe Iymphoplasmacytic in- filtration including many CD4-positive or CD8-positive T lymphocytes and IgG4-positive plasma cells （≥10/HPF）, was observed in the major duodenal papilla of all 3 patients with AIR The same findings were also detected in the biopsy specimens taken from the major duodenal papilla of 2 patients with/kiP, but in controls, there were only a few （≤3/HPF） IgG4-positive plasma cells infiltrating the major duodenal papilla. CONCLUSIONS： An abundant infiltration of IgG4-positive plasma cells is specifically detected in the major duodenal papilla of patients with A/P. Although this is a preliminary study, IgG4-immunostaining of biopsy specimens taken from the major duodenal papilla may support the diagnosis of AIR