Effect of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on identifing biomarkers of endometriosis

Background Endometriosis is a common gynecological disease. This study aimed to screen proteins that were expressed differently in patients with endometriosis versus normal controls using proteomic techniques, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF-MS）.
Methods Protein chip SELDI-TOF-MS combines the advantages of microarray and mass spectrometry, and can screen latent markers in sera of patients with endometriosis. Serum samples from patients and normal volunteers were analyzed by SELDI-TOF-MS.
Results After comparing the serum protein spectra of 36 patients with 24 normal controls, 24 differently expressed potential biomarkers （P 〈0.01） were identified. Using Biomarker Pattern software, we established a tree model of the 60 serum protein spectra. When using the three bJomarkers to classify the samples, the sensitivity for diagnosing endometriosis was 91.7%, specificity was 95.8%, and coincidence rate was 93.3%. Then we used serum samples from 12 patients and 8 normal controls to validate the tree model and report the sensitivity for diagnosing endometriosis was 91.7%, specificity was 75%, and coincidence rate was 85%.
Conclusions SELDI-TOF-MS may be a useful tool in high-risk population screening for endometriosis. The identification and application of the biomarkers need to further study.     

Magnetic resonance study of the structure and function of the hippocampus and amygdala in patients with depression

Background The hippocampus and amygdala exhibit structural and functional alterations in patients with depression. The objective of this study was to investigate the structural and functional relationships between these core regions. Methods Based on the severity of their condition, 60 patients and 20 healthy controls were equally divided into four groups （mild group, moderate group, major group and health controls group）, scanned by T1-MR, functional magnetic resonance imaging （fMRI）, and susceptibility weighted imaging （SWI）. Structural image, BOLD image, and SWI image were collected for processing and analysis. The characteristics of the depression and controls were checked by analysis of variance test, and the difference between groups was checked by Dunnett＇s test. Results The volume of hippocampus and amygdala varied with the severity of the condition. The signal obtained under the stimulation of negative events was linearly decreased in the mild, moderate and major groups revealed by fMRI. The length and diameter of the lateral ventricle vein was reduced in the mild group, whereas the number of branches increased. In the moderate and major groups, the reduction in the length, diameter and increase in the number of branches of the lateral ventricle vein were greater. Conclusion The alterations of the volume, fMRI, and cerebral veins in these core regions may account for the causal relationship between structure and function.     

Relationship between Single Nucleotide Polymorphisms in -174G/C and -634C/G Promoter Region of Interleukin-6 and Prostate Cancer

The association between the single nucleotide polymorphisms （SNPs） in -174G/C and -634C/G of interleukin-6 （IL-6） promoter region and prostate cancer was examined in the population of Han people in Hubei region. TaqMan PCR was employed for the gene-typing of -174G/C and -634C/G in promoter region of IL-6 gene to compare the prostate cancer patients and normal controls in terms of genotype frequency, allele frequency and risk of prostate cancer. Enzyme-linked immu- nosorbent assay （ELISA） was used for the detection of IL-6 concentration in peripheral blood of the patients with prostate cancer and the relationship between the IL-6 level and the genotype was studied. Our results showed that in all the subjects, the genotype of genetic locus -174G/C was found to be GG and no CG and CC were observed. There was a significant difference in gene frequency of GG, CG and CC of -634C/G and allele frequency of G and C between prostate cancer patients and normal controls （P〈0.05） and the gene frequency of GG＋CG increased with the clinical stages and pathological grades of prostate cancer. The IL-6 level in GG＋CG group was significantly higher than that in CC group. It was concluded that no SNP in -174G/C IL-6 promoter region was found in the population of Han people in Hubei region. The SNP in -634C/G was, to some extent, associated with the development and progression of prostate cancer. The population with GG＋CG genetype has higher risk for prostate cancer.     

Application of serum protein fingerprinting coupled with artificial neural network model in diagnosis of hepatocellular carcinoma

Background Hepatocellular carcinoma tends to present at a late clinical stage with poor prognosis. Therefore, it is urgent to explore and develop a simple, rapid diagnostic method, which has high sensitivity and specificity for hepatocellular carcinoma at an early stage. In this study, the serum proteins in patients with hepatocellular carcinoma or liver cirrhosis and in normal controls were analysed. Surface enhanced laser desorption/ionization time-of-flight mass (SELDI-TOF-MS) spectrometry was used to fingerprint serum protein using the protein chip technique and explore the value of the fingerprint, coupled with artificial neural network, to diagnose hepatocellular carcinoma.Methods Of the 106 serum samples obtained, 52 were from patients with hepatocellular carcinoma, 22 from patients with liver cirrhosis and 32 from healthy volunteers. The samples were randomly assigned into a training group (n=70, 35 patients with hepatocellular carcinoma, 14 with liver cirrhosis, and 21 normal controls) and a testing group (n=36, 17 patients with hepatocellular carcinoma, 8 with liver cirrhosis, and 11 normal controls). An artificial neural network was trained on data from 70 individuals in the training group to develop an artificial neural network diagnostic model and this model was tested. The 36 sera in the testing group were analysed with blind prediction by using the same flowchart and procedure of data collection. The 36 serum protein spectra were clustered with the preset clustering method and the same mass/charge (M/Z) peak values as those in the training group.　 Matrix transfer was performed after data were output. Then the data were input into the previously built artificial neural network model to get the prediction value. The M/Z peaks of the samples with more than 2000 M/Z were normalized with biomarker wizard of ProteinChip Software version 3.1 for noise filtering. The first threshold for noise filtering was set at 5, and the second was set at 2. The 10% was the minimum threshold for clustering. The statistical analysis of the data of serum protein mass spectrum was performed in the groups (normal vs. hepatocellular carcinoma, and liver cirrhosis vs. hepatocellular carcinoma) with the t test. Results Comparison between the groups of hepatocellular carcinoma and normal control: The mass spectra from 56 samples (hepatocellular carcinoma and normal controls) in the training group were analysed and 241 peaks were obtained. In addition, 21 peaks from them were used for comparison between the groups of hepatocellular carcinoma and normal controls (P<0.01). Only 2 peaks at 3015 M/Z and 5900 M/Z were selected with significant difference ［P<10（-9）］. A model was developed based on these two proteins with different M/Z. It was confirmed that this artificial neural network model can be used for comparison between the groups of hepatocellular carcinoma and normal controls. The sensitivity was 100% (17/17), and the specificity was 100% (11/11). Comparison between the groups of hepatocellular carcinoma and liver cirrhosis: The mass spectra from 49 samples in the training group (including patients with hepatocellular carcinoma and liver cirrhosis) were analysed and 208 peaks were obtained. In addition, 21 peaks from them were used for comparison between the groups of hepatocellular carcinoma and liver cirrhosis (P<0.01). Only 2 peaks at 7759 M/Z, 13134 M/Z were selected with significant difference ［P<10（-9）］. A model was developed based on these two proteins with dfferent M/Z. It was confirmed that this artificial neural network model can be used for comparison between the groups of hepatocellular carcinoma and liver cirrhosis. The sensitivity was 88.2% (15/17), and the specificity was 100% (8/8).Conclusions The specific biomarkers selected with the SELDI technology could be used for early diagnosis of hepatocellular carcinoma.     

Assessment of Left Ventricular Global Twist in Essential Hypertensive Heart by Speckle Tracking Imaging

The left ventricular twist was evaluated by 2-dimensional ultrasound speckle-tracking imaging （STI） in 50 patients with hypertension with normal geometric left ventricle （LV） and 45 normal subjects as control group. The mean value of LV rotation was obtained at each plane Using STI. LV twist and twist velocity were defined as apical rotation/rotation rate relative to the base respectively. To adjust the intersubject differences in heart rates, the time sequence were normalized. The results showed that peak twist developed near the end of systole. Peak LV twist was significantly higher in patients with hypertension than normal controls （P〈0.001）. The diastolic untwisting mainly occurred in early diastole （=38%）. Compared with normal controls, untwisting rate （Untw R） in patients with hypertension was significantly reduced （P〈0.001）, and untwisting half-time （UHT） was significantly delayed （P〈0.05）. This study demonstrated that STI has a potential ability to evaluate the early change of heart function in patients with hypertension by measuring the twist of LV.     

Clinical Characteristics of Paroxysmal Kinesigenic Choreoathetosis： Diagnosis, Treatment and Prognosis

The clinical characters, diagnosis and differential diagnosis of paroxysmal kinesigenic choreoathetosis （PKC）, and efficacy of the anti-epileptic drugs （AEDs） were investigated. Thirty-one patients with PKC were collected, and the clinical characters and change of EEG were analyzed. The average age of the first attack was 16.8 years old and the pinnacle was 10 to 20 years old. There were definite causes for every attack and the sudden the whole attack was always less than 1 min. movement was the most common one （92%）. Time for The attack presented with muscle tension disturbance （83.9%）, movement like dancing （16.1%）, abnormal movement of mouth and face and other symptoms （16.2%）. The attack tended to be very frequent and 71% patients were beyond once per day. The EEG examination and image scan of primary PKC were normal in most patients. Low dosage of AEDs could control the attack of 50%-77.3% patients. It was concluded that PKC was a common disease of movement disorder. The therapy by AEDs was very effective. PKC should be differentiated from epilepsy and the relationship between PKC and epilepsy needs further research.     

Circulating adhesion molecules in patients with Keshan disease and their relationship with Coxsackie B virus infection

This study determined the levels of serum soluble intercellular adhesion molecule-1 （sI-CAM-l） and soluble vascular cell adhesion molecular-1 （sVCAM-1） in patients with different types of Keshan disease （KD）, examined the relationship between Coxsackie B virus-specific IgM antibody （CBV-IgM） and slCAM-1 or sVCAM-1 in KD patients, and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications. The levels of serum slCAM-1, sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease （CKD）, 27 with latent Keshan disease （LKD） and 28 healthy controis. The subjects in different groups were adjusted for sex and age. Echocardiography was adopted to determine left ventricular ejection fraction （LVEF） in 22 patients with CKD. The results showed that CKD patients had significantly higher levels of slCAM-1 and sVCAM-1 than LKD patients and healthy controls （P〈0.01 for all）. And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls （P〈0.05）. A negative correlation was found between LVEF and slCAM-1 or sVCAM-1 in CKD patients. The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls. In CVB-specific IgM positive patients, the levels of serum slCAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart. It was concluded that the increase in the levels of slCAM-1 and sVCAM-1 suggests the progression of inflammation in KD. slCAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum slCAM-1 and sVCAM-1 in KD patients may be related to CBV infection.     

Differences in P50 and prepulse inhibition of the startle reflex between male smokers and non-smokers with first episode schizophrenia without medical treatment

Backgorund Nicotine may improve schizophrenia patient＇s cognitive deficit symptoms.This study was to explore the chronic effects of smoking on prepulse inhibition of the startle reflex （PPI） and P50 in the patients with first-episode schizophrenia （FES）.Methods The event-related potentials （ERP） recording and analysis instrument made by Brain Products,Germany,was used to detect PPI and P50 in 49 male FES patients （FES group,n=21 for smokers and n=28 for non-smokers） and 43 normal male controls （control group,n=19 for smokers and n=24 for non-smokers）.Results Compared with normal controls,the FES group had prolonged PPI latency when elicited by single stronger stimulus （P ＜0.05）; the FES group had prolonged PPI latency and increased PPI amplitude （P ＜0.05,0.01） when elicited by weak and strong stimuli.The FES group had lower PPI inhibition rate than normal controls （P ＜0.05）.Compared with normal controls,the FES group had increased P50-S2 amplitude and increased amplitude ratio S2/S1 （both P ＜0.05）.In the control group,the smokers had a tendency of increase in P50-S2 amplitude （P ＞0.05） and shorter P50-S2 latency （P ＜0.05） than the non-smokers.The smokers had higher PPI amplitude than the non-smokers （P ＜0.05）.In the FES group,the smokers had higher P50-S1 amplitude,shorter P50-S2 latency,and higher amplitude ratio S2/S1 than the non-smokers （P ＜0.05,0.01）.The smokers had higher PPI amplitude than the non-smokers （P ＜0.05）.Conclusions There is obvious PPI and P50 deficits in schizophrenic patients.However,these deficits are relatively preserved in the smokers compared with the non-smokers,which suggests that long-term smoking might partially improve the sensory gating in schizophrenic patients.Whether this conclusion can be deduced to female patients requires further follow-ups.     

Perilipin Gene 1237 T＞C Polymorphism is not Associated with Obesity Risk in Northern Chinese Han Adults

Objective To identify the association between PLIN 1237 polymorphism and obesity in Chinese Han adults. Methods A total of 994 adults （157 obese subjects, 322 overweight subjects, and 515 normal controls） were recruited from two rural communities. PLIN 1237 polymorphism was genotyped by polymerase chain reaction-restriction-fragment-length-polymorphism （PCR-RFLP）. Association between PLIN polymorphisms and obesity status was estimated by ordinal logistic regression. Results The three genotypes of,PLIN 1237 were detected with a percentage of 54.3%, 37.1%, and 8.6% in TT, TC, and CC genotypes, respectively. For the PLIN 1237 polymorphism locus, the frequency of alleles T and C was 0.73 and 0.27, respectively. The PLIN 1237 polymorphisms were in Hardy-Weinberg equilibrium. PLIN 1237 polymorphism was not associated with obesity. The odds ratio for overweight or obesity for the CC＋TC genotype was 0.8（0.4, 1.4） in women （P=-0.4） and 0.6 （0.3, 1.3） in men （P=-0.2） after adjustment for age, education, household income and alcohol consumption, smoking, and physicalactivity. Conclusion Chinese Han adults have a lower frequency of variant-allele C in PLIN1237. PLIN1237 T〉C polymorphism is not significantly associated with obesity in northern Chinese adults.     

Saffron （Crocus sativus L.） and major depressive disorder： a meta-analysis of randomized clinical trials

Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder （MDD）. Of these, accumulating trials reveal positive effects of the spice saffron （Crocus sativus L.） for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted. OBJECTIVE： The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD. SEARCH STRATEGY： We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies. INCLUSION CRITERIA： The criteria for study selection included the following： （1） adults （aged 18 and older） with symptoms of depression, （2） randomized controlled trial, （3） effects of saffron supplementation on depressive symptoms examined, and （4） study had either a placebo control or antidepressant comparison group. DATA EXTRACTION AND ANALYSIS： Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta- analysis 2 was used to analyze the data. RESULTS： Based on our pre-specified criteria, five randomized controlled trials （n = 2 placebo controlled trials, n = 3 antidepressant controlled trials） were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms （M ES = 1.62, P 〈 0.001）, revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation and the antidepressant groups （M ES = -0.15） indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials. CONCLUSION： Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron＇s efficacy and safety for treating depressive symptoms.     

Association between intervertebral disc degeneration and disturbances of blood supply to the vertebrae

Low back pain is a common public health problem in western industrialized societies and the world as well.Studies indicate that the prevalence rate ranges to 35%, with around 10% of patients from 12% becoming chronically disabled. It also places an enormous economic burden on society. Although the exact cause of low back pain has yet to be defined, intervertebral disc degeneration is considered a major source of it. Since patients with degenerative discs are often asymptomatic, the mechanisms of it are still unclear.     

Relevance of muscle biopsy for diagnosing multifocal motor neuropathy

Multifocal motor neuropathy （MMN） is a rare,.focal,inflammatory,demyelinating disease of the peripheral nerves with pure motor involvementJ MMN is clinically characterized by slowly progressive,asymmetric,distal,upper limb predominant weakness,in the absence of sensory disturbances） Weakness is usually multifocal and connected to a distinct motor nerve,such as the musculocutaneous nerve resulting in biceps weakness,the posterior interosseus nerve resulting in finger drop,the median,ulnar,or radial nerve resulting in dexterity problems or grip weakness,or the peroneal nerve resulting in a foot drop.Onset of clinical manifestations is between 20 and 50 years of age.The prevalence of MMN is reported as 1-2 per 100 000.2 MMN is three times more frequent in men as compared to women.     

痘苗病毒天坛株的减毒与其作为疫苗载体研究进展

1痘苗病毒天坛株的历史天花是人类历史上最可怕的传染病之一。天花由天花病毒（variola virus）引起,人是该病毒的惟一宿主。人感染天花病毒后的死亡率达到30%~40%[1]。世界上公认的对天花最早的准确记录来自中国,晋代药学家葛洪于公元430年左右,在《肘后备急方》中对天花有清楚的描述[1]。     

Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis： study protocol of a multicenter randomized controlled trial

BACKGROUND： Rheumatoid arthritis （RA）, as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA. METHODS AND DESIGN： This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1：1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo （imitation leflunomide）. The control group will receive leflunomide and an herbal placebo （imitation Xinfeng Capsule）. The American College of Rheumatology （ACR） Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate （ACR20）, which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment. DISCUSSION： The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA. TRIAL REGISTRATION： This trial has been registered in ClinicalTrials.gov. The identifier is N CT01774877.     

WHO西太区与世界中医药学会联合会中医名词术语国际标准比较研究：八纲辨证（三）

The Chinese characters 寒 and 热, 虚, and 实 are quite common concepts in Chinese language. However in traditional Chinese medicine （TCM）, they are used as four principles in syndrome differentiation. In terms of translation, 寒 and 热 are very easy to understand and can be simply translated as ＂cold＂ and ＂heat＂. But the transla- tion of 虚 and 实 used to be a problem. For a quite long time in translation practice,     

Gene expression profiles of ERCC1, TYMS, RRM1, TUBB3 and EGFR in tumor tissue from non-small cell lung cancer patients

Background Personalized medicine becomes essential in lung cancer treatment, however lung-cancer-related gene expression profiles in Chinese patients remain unknown. In this study, the correlation of gene expression profiles and clinical characteristics in non-small-cell lung cancer （NSCLC） was investigated. Methods Seventy-six Chinese patients with NSCLC were enrolled in the study to investigate mRNA expression profiles of excision repair cross complement group 1 （ERCC1）, thymidylate synthetase （TYMS）, ribonucleotide reductase （RRM1）, class Ill 13-tubulin （TUBB3）, and epidermal growth factor receptor （EGFR） genes and their correlation with patient clinical characteristics. A novel liquidchip technology was used to detect mRNA expression levels in formalin fixed paraffin embedded tumor pathology samples. The relationships between gene expression and clinical characteristics were assessed using the Mann-Whitney test. Results ERCC1 mRNA levels were higher in tumors from patients with metastatic disease than patients with non- metastatic disease （P=-0.021）, and higher in adenocarcinomas than squamous cell carcinomas （P=0.006）. Increased TUBB3 mRNA expression levels were found in patients with performance status （PS） 1 in comparison with PS 0 （P=0.049）, with poorly differentiated tumors in comparison with tumors that were moderately and well differentiated （P 〈0.000 1）, and with advanced stage in comparison with early stage disease （P 〈0.000 1）. Conclusions ERCC1 mRNA levels were higher in metastatic adenocarcinoma NSCLC; TUBB3 mRNA levels were significantly higher in poorly differentiated tumors and in advanced stage NSCLC, which indicates the poor prognosis.     

高维列联表资料的统计分析与SAS软件实现（六）

非条件logistic回归分析方法的主要算法是采用最大似然法对参数进行估计。最大似然法在大样本前提下进行参数估计是非常有效的,但当处理样本量小的数据,特别是按多个定性变量进行分层且每一层中样本量很小时,