“抗体平”对抗精子抗体阳性男性不育患者精子膜结构的影响

“抗体平”对抗精子抗体阳性男性不育患者精子膜结构的影响是1997年北京市中医药管理局中医药科技项目资助的研究课题。我们经过3年多的研究，按申请书（合同书）的要求，共观察60例抗精子抗体阳性男性不育患者服用中药“抗体平”（陈文伯方）前后血清中抗精子抗体和电子显微镜下经冷冻蚀刻后精子膜结构的变化（使用中国科学院生物物理研究所实验设备和技术），对“抗体平”治疗抗精子抗体阳性男性不育患者的疗效进行分析评价。现将研究结果总结报告如下。

Establishment and Preliminary Application of a Rapid Fluorescent Focus Inhibition Test (RFFIT) for Rabies Virus

The World Health Organization (WHO) standard assay for determining levels of the rabies virus neutralization antibody (RVNA) is the rapid fluorescent focus inhibition test (RFFIT), which is used to evaluate the immunity effect after vaccination against rabies. For RFFIT, CVS-11 was used as the challenge virus, BSR cells as the adapted cells, and WHO rabies immunoglobulin (WHO STD) as the reference serum in this study. With reference to WHO and Pasteur RFFIT procedures, a micro-RFFIT procedure adapted to our laboratory was produced, and its specificity and reproducibility were tested. We tested levels of RVNA in human serum samples after immunization with different human rabies vaccines (domestic purified Vero cell rabies vaccine (PVRV) and imported purified chick embryo cell vaccine (PCECV)) using different regimens (Zagreb regimen and Essen regimen). We analyzed the levels of RVNA, and compared the immune efficacy of domestic PVRV and imported PCECV using different immunization regimens. The results showed that the immune efficacy of domestic PVRV using the Zagreb regimen was as good as that of the imported PCECV, but virus antibodies were generated more rapidly with the Zagreb regimen than with the Essen regimen. The RFFIT procedure established in our laboratory will enhance the comprehensive detection ability of institutions involved in rabies surveillance in China.

Thiazide-associated hyponatremia in the elderly： what the clinician needs to know

Thiazide-induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. This review presents the current evidence regarding the thiazide-associated hyponatremia. Thiazide-associated hyponatremia is observed mainly in patients with certain risk factors such as those receiving large doses of thiazides, having much comorbidity, such as heart failure, liver disease or malignancy, and taking several medications, such as non-steroidal anti-inflammatory drugs, selective serotonin re-uptake inhibitors or tricyclic antide- pressants. Sodium concentration should be monitored in patients with risk factors for developing thiazide-associated hyponatremia and clini- cians should measure promptly serum sodium levels in patients with neurologic signs indicating reduced sodium levels. The clinical and biochemical profile of patients with thiazide-associated hyponatremia may be that of extracellular volume depletion or the syndrome of inap- propriate antidiuretic hormone secretion （SIADH）. The investigation of possible thiazide-associated hyponatremia includes the exclusion of other causes of decreased sodium levels and the identification of the characteristics of hyponatremia due to thiazides （extracellular volume depletion-related or SIADH-like）. Treatment should be carefully monitored to avoid serious neurologic complications due to overcorrection. Clinicians should discourage prescribing thiazides in patients with a history of diuretic-associated hyponatremia and should prefer low doses of thiazides in patients with risk factors for developing thiazide-associated hyponatremia.

Endomysial antibodies predict celiac disease irrespective of the titers or clinical presentation

AIM:To investigate the association between serum antibody levels and a subsequent celiac disease diag-nosis in a large series of children and adults. METHODS:Besides subjects with classical gastrointestinal presentation of celiac disease,the study cohort included a substantial number of individuals with extraintestinal symptoms and those found by screening in at-risk groups.Altogether 405 patients underwent clinical,serological and histological evaluations.After collection of data,the antibody values were further graded as low[endomysial(EmA)1:5-200,transglutaminase 2 antibodies(TG2-ab)5.0-30.0 U/L]and high (EmA 1:≥500,TG2-ab≥30.0 U/L),and the serological results were compared with the small intestinal mucosal histology and clinical presentation. RESULTS:In total,79%of the subjects with low and 94%of those with high serum EmA titers showed small-bowel mucosal villous atrophy.Furthermore, 96%of the 47 EmA positive subjects who had normal mucosal villi and remained on follow-up either subsequently developed mucosal atrophy while on a glutencontaining diet,or responded positively to a glutenfree diet. CONCLUSION:Irrespective of the initial serum titers or clinical presentation,EmA positivity as such is a very strong predictor of a subsequent celiac disease diagnosis.

Analysis of Serum Levels of IgA Antibodies to Epstein Barr Virus Capsid Antigens in the Spouses and the Children of Patients with Nasopharyngeal Carcinoma

OBJECTIVE To analyze the serum levels of IgA antibodies to Epstein Barr virus capsid antigens （EBV/IgA/VCA） in patients with nasopharyngeal carcinoma （NPC） and in their spouses and children in order to further evaluate the risk of developing the disease in family members of NPC patients. METHODS Four categories of sera were used to detect EBV/ IgA/VCA using the immunoenzyme method. In our study 317 biopsy-confirmed NPC patients, 317 spouses and 317 children of the NPC patients, as well as 413 healthy subjects as the controls that came from the same area were enrolled. RESULTS The positive rate of EBV/lgA/VCA was 97.2%, 14.2%, 19.9% and 3.1% in the NPC patients, the spouse and child groups, and in the control group, respectively. The positive rate was significantly higher in the NPC group than in the other 3 groups, and it was also significantly higher in the spouse and in the child groups than in the control group （P 〈 0.001）. The results of the relative to identified distribution unit （Ridit） analysis showed that the average Ridit values were 0.860, 0.404, 0.424 and 0.356 respectively in the NPC patients, in the spouse and child groups, and in the control group. The antibody titer of IgA/VCA was significantly higher in the NPC group than in the other 3 groups, and it was also significantly higher in both the spouse and child groups than in the control group （P 〈 0.001）. The OR values of positive EBV/IgA/VCA antibody were 5.09 and 7.63, respectively in the spouse and child groups. No significant differences were found in the positive rates or in the titers of IgA/VCA antibody between the groups of spouses and children （P 〉 0.05）. CONCLUSION Positive detection of EBV/IgA/VCA antibody occurs in familial aggregation, as there is ample opportunity for EBV reactivation in the spouses and in the children of NPC patients. These individuals with a high risk of developing the NPC should be closely followed in order to detect the disease at an early stage.

Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease.METHODSLevels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays.RESULTSWe found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH.CONCLUSIONAuto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other.

Genetic Analysis of the P1 Region of Human Enterovirus 71 Strains and Expression of the 55 F StrainVP1 Protein

Enterovirus 71 （EV71） is a member of the Entero-virus genus of the Picomaviridae family and is the major cause of Hand, foot, and mouth disease （HFMD） in children. Different strains from Gansu were cloned and the P1 protein was sequenced and analysed. Results indicate that there are three kinds of EV71 infections prevalent in Gansu. The VP 1 protein from one of these strains, 55F, was expressed. The recombinant protein was expressed with high level and reacted specifically with the EV71 patient antibody, the recombinant protein was also applied to raise antiserum in rabbits and after the fourth injection a high titer of antiserum was detected by ELISA assay. These data are useful for further clarification of prevalent EV71 strains in the north of China at the molecular level and provide a basis for EV71 diagnosis.

Prevalence of Anti-HCV Antibodies Among Thalassemia Patients in Mosul City, Iraq

The study included 200 thalassemia patients, 120 （60%） males and 80 （40%） females, at age 2-30 years the mean age 16 years and 100 persons from blood donors at age 20-50 years, the mean age 35 years, as control group. The authors used ELISA HCV 3.0 to detect anti-HCV in serum of thalassemia patients and blood donors. The results show 17% positive, 76% negative and 7% equivocal in serum ofthalassemia patients, but show 1% positive, 98% negative, 1% equivocal in serum of blood donors. The results show significant difference in P ≤ 0.05 between prevalence of anti-HCV antibodies among thalassemia patients and blood donors, the confirmatory tests by recombinant immunoblot assay version 3.0 （RIBA） show 17.5% positive, 79% negative and 3.5% equivocal in serum of thalassemia patients but show 2% positive, 98% negative in serum of blood donors. The thalassemia patients in the present study region had high seroprevalence of anti-HCV.

Seroprevalence of anti-HAV among patients with chronic viral liver disease

AIM:To investigate the current seroprevalence of hepatitis A virus(HAV) antibodies in patients with chronic viral liver disease in Korea.We also tried to identify the factors affecting the prevalence of HAV antibodies. METHODS:We performed an analysis of the clinical records of 986 patients(mean age:49±9 years,714 males/272 females) with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection who had undergone HAV antibody testing between January 2008 and December 2009.RESULTS:The overall prevalence of IgG anti-HAV was 86.61%(854/986) in patients with chronic liver disease and was 88.13%(869/986) in age-and gendermatched patients from the Center for Health Promotion.The anti-HAV prevalence was 80.04%(405/506) in patients with chronic hepatitis B,86.96%(20/23) in patients with chronic hepatitis C,93.78%(422/450) in patients with HBV related liver cirrhosis,and 100%(7/7) in patients with HCV related liver cirrhosis.The anti-HAV prevalence according to the decade of age was as follows:20s(6.67%) ,30s(50.86%) ,40s(92.29%) ,50s(97.77%) ,and 60s(100%) .The antiHAV prevalence was significantly higher in patients older than 40 years compared with that in patients younger than 40 years of age.Multivariable analysis showed that age≥40 years,female gender and metropolitan cities as the place of residence were independent risk factors for IgG anti-HAV seropositivity. CONCLUSION:Most Korean patients with chronic liver disease and who are above 40 years of age have already been exposed to hepatitis A virus.

Expression of proto-oncogene Fra-1 in human neoplastic breast tissues

Objective： Invasion and metastasis are the most significant and intrinsic biological characteristics of cancers, also which are main factors of malignant tumor causing treatment failure and death. Recent studies have found that Fra-1 plays an important role on cell migration, invasion, and maintaining malignant phenotype of transformed cells. But there are few stud- ies about the expression and location of Fra-1 in breast tissues and cells being reported .This study just aims to discuss the expression and location of transcription factor Fra-1 in benign and malignant human breast tissues. Methods： The expression of Fra-1 was investigated by immunohistochemistry in neoplastic breast diseases ranging from benign fibroadenoma to very aggressive undifferentiated carcinoma. The correlations of Fra-1 expression with other indicators of breast carcinoma prog- nosis （ER, PR and ErbB2 receptors） were analyzed. Results： All neoplastic breast tissues, either benign or malignant breast tissues, were nuclear immunoreactive for Fra-l-recognizing antibody. In 85% of benign tumors （17/20）, the immunoreactive for Fra-l-recognizing antibody as exclusively restricted to the nuclei. In three cases （3/20, 15%）, focal unequivocal cytoplas- mic staining was also exhibited. Strong positive nuclear staining for Fra-1 was easily seen in all types of breast carcinomas. However the nucleaflcytoplasmic concomitant immunoreactivity was observed in all types of breast carcinomas. A clear shift in Fra-1 immunoreactivity, from an exclusively nuclear to a simultaneous nuclear and cytoplasmic localization was noticed in 90.2% （37/41） of breast carcinomas. No inverse relationship between Fra-1 and ER and PR protein levels was noticed in malignant tumors. The relative expression level of Fra-1 was not correlated with the expression of ErbB2. Conclusion： The overall expression, pattern and intensity of Fra-1 proteins were correlated with breast oncogenesis. Overexpression of Fra-1, leading to a persistent high cytoplasmic accumulation, may play a role in the process of breast carcinogenesis.

Viral suppression of innate immunity via spatial isolation of TBK1/IKKε from mitochondrial antivirai platform

For antiviral signaling mediated by retinoic acid-inducible gene I （RiG-I）-like receptors （RLRs）, the recruitment of cytosoUc RLRs and downstream molecules （such as TBK1 and IKKε） to mitochondriaL platform is a central event that facilitates the establishment of host antiviral state. Here, we present an example of viral targeting for immune evasion through spatial isolation of TBK1/IKKε from mitochond riai antiviral platform, which was employed by severe fever with thrombocytopenia syndrome virus （SFTSV）, a deadly bunyavirus emerging recently. We showed that SFTSV nonstructural protein NSs functions as the interferon （IFN） antagonist, mainly via suppressing TBK1/IKKε-IRF3 signaling. NSs mediates the formation of cytoplasmic inclusion bodies （IBs）, and the blockage of IB formation impairs IFN-inhibiting activity of NSs. We next demonstrate that I Bs are utilized to compartmentalize TBK1/I KKε. The compartmentalization results in spatial isolation of the kinases from mitochondria, and deprived TBK1/IKKε may participate in antiviral complex assembly, leadingto the blockage of lFN ind uction. This study proposes a new role of viral I Bs as virus-built＇jail＇ for imprisoning cellular factors and presents a novel and likely common mechanism of viral immune evasion through spatial isolation of critical signaling molecules from the mitochondrial antiviral platform.

Effects of mass layer imperfect bonding on the electrical impedance of a quartz crystal microbalance

We study electrically forced vibrations of a crystal plate of AT-cut quartz carrying a thin mass layer operating as a quartz crystal microbalance for mass sensing.The mass layer is imperfectly bonded to the crystal plate with their interface described by the so-called interface-slip model which allows a discontinuity of the tangential interface displacement.Mindlin’s equations for piezoelectric plates are used.An analytical solution is obtained.The electrical impedance is calculated.The effects of an elastic interface and a viscoelastic interface are examined.

Interface stress element method and its application in analysis of anti-sliding stability of gravity dam

The rigid body limit equilibrium method （LEM） and the nonlinear finite element method （NFEM） are often used in the analysis of anti-sliding stability of gravity dam. But LEM cannot reflect the process of progressive instability and mechanical mecha- nism on failure for rock mass while NFEM is difficult to use to solve the displacement discontinuity of weak structural plane. Combining the research with Xiangjiaba Hydropower Station project, the analysis of anti-sliding stability for segment 12# of the dam has been carried out using interface stress element method （ISEM）. The results can reflect the most dangerous location, the scope and distribution of failure zone in weak structural plane, and present the process of progressive failure in dam foun- dation as well as the safety coefficient of possible sliding body. These achievements provide an important technical reference for dam foundation treatment measures. The computational results show that ISEM can naturally describe discontinuous de- formation of rock mass such as dislocation, openness and sliding. Besides, this method is characterized by good adaptability, convenient calculation and high compatibility, thus it is regarded as an effective way to make an analysis of anti-sliding stabil- ity of gravity dam