目的 分析原发性胆汁性肝硬化(PBC)实验室指标,为临床诊治提供依据.方法 选取2016年解放军第三〇二医院诊断为PBC的患者593例,对其自身抗体指标抗线粒体抗体(AMA)、抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗线粒体抗体-M2(AMA-M2)、抗可溶性肝抗原/肝胰抗原抗体(SLP)、抗核孔复合物糖蛋白210抗体(gp210)、核点型靶抗原蛋白(Sp100)、早幼粒白血病蛋白(PML)以及生化免疫学指标谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、免疫球蛋白 A (IgA)、免疫球蛋白 M(IgM)、免疫球蛋白 G(IgG)进行检测并分析结果.结果 PBC患者血清内 ANA、AMA、SMA、AMA-M2、SLP/LP、gp210、Sp100的检出率显著高于慢性乙型肝炎组,差异均有统计学意义(P<0.05).ANA的主要核型是核膜型(225例,52.33%)以及核点型(90例,20.93%),滴度以中高滴度为主(≥1:320),复合核型也有相当比例(113例,26.28%).AM A以高滴度(≥1:1000)为主(470例,84.79%).AM A-M2的滴度以高滴度(≥"3+")为主(358例, 88.18%).PBC组患者的GGT、ALP、IgM、IgG与慢性乙型肝炎组患者比较均显著升高,差异有统计学意义(P<0.05), IgA差异无统计学意义(P>0.05).结论 各型自身抗体对于 PBC具有诊断意义,ALP、GGT、IgM 不明原因升高也是PBC特殊指征,临床应该重视各种实验室指标,对于PBC患者早诊断早治疗,积极改善PBC患者的生存质量.

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor evolved from cirrhosis. It is quite significant to seek accurate, easy markers for early warning and diagnosis of HCC. Through prospective cohort follow-up study and mass spectrometry, we discovered and verified a serum marker valuable for early warning and diagnosis. Follow-up observation was performed on cirrhosis patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was adopted to detect the serums of patients, and the serum polypeptides with a potential value in early HCC warning and diagnosis were screened. Electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF-MS/MS) was exploited to identify these screened polypeptides. Moreover, the serum marker concentration was determined by ELISA to validate the clinical value of the serum marker. Among 109 cirrhosis patients followed up for two years, 29 patients (26.6%) finally progressed into HCC. MALDI-TOF MS shows that the concentration of a 3155.66Da polypeptide was significantly different between the patients that progressed into HCC and those not. Through MS/MS identification, it is confirmed that the polypeptide is inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4). The serum ITIH4 concentrations in two groups were measured with ELISA and compared with Alpha-fetoprotein (AFP). Results show that serum ITIH4 and AFP concentrations were negatively correlated (r=−0.263, p=0.0006), and the ITIH4 concentration had a significant intergroup difference (p=0.000). Receiver operating characteristic (ROC) curve indicates that its predictive value (area under the curve, AUC) is 0.667, superior to AFP. For the patients progressing into HCC, serum samples were separately collected when they were recruited and diagnosed as cirrhosis. Measurement on these samples reveals that ITIH4 was declining during the progression of HCC (p=0.006). By virtue of mass spectrometry, we discovered and identified a biomarker valuable for early HCC warning and diagnosis. This marker overperforms the commonly used AFP, demonstrating a bright prospect.

The early prediction values of diagnostic markers for hepatocellular carcinoma (HCC) are still unclear at present. This study evaluated the prediction value of ten serum markers in HCC. A total of 109 cases of hepatic cirrhosis patients were followed up for 36 months and the relationship between the lifetime risk of developing HCC and levels of serum markers was analyzed. 31.2 (34/109) percent of hepatic cirrhosis patients developed HCC during the study’s timeframe. Higher alpha-fetoprotein (AFP), alpha-fetoprotein-L3 (AFP-L3), alanine aminotransferase (ALT), and AFP-L3/AFP ratio levels are potential risk factors for malignization in hepatic cirrhosis patients (RR=2.99, 2.92, 2.72, and 2.34); serum Golgi protein 73 (GP73) level of hepatic cirrhosis patients decreased significantly after developing HCC (t=2.212;p=0.041). The detection of ALT, AFP, AFP-L3, and GP73 has a certain guiding significance to predict the risk of HCC in hepatic cirrhosis patients.

Background: Differentiation of malignant from benign liver tumors remains a challenging problem. In recent years, mass spectrometry (MS) technique has emerged as a promising strategy to diagnose a wide range of malignant tumors. The purpose of this study was to establish classification models to distinguish benign and malignant liver tumors and identify the liver cancer-specific peptides by mass spectrometry.Material/ Methods: In our study, serum samples from 43 patients with malignant liver tumors and 52 patients with benign liver tumors were treated with weak cation-exchange chromatography Magnetic Beads (MB-WCX) kits and analyzed by the Matrix-Assisted Laser Desorption Time of Flight Mass Spectrometry (MALDI-TOF-MS). Then we established genetic algorithm (GA), supervised neural networks (SNN), and quick classifier (QC) models to distinguish malignant from benign liver tumors. To confirm the clinical applicability of the established models, the blinded validation test was performed in 50 clinical serum samples. Discriminatory peaks associated with malignant liver tumors were subsequently identified by a qTOF Synapt G2-S system.Results: A total of 27 discriminant peaks (p<0.05) in mass spectra of serum samples were found by ClinPro Tools software. Recognition capabilities of the established models were 100% (GA), 89.38% (SNN), and 80.84% (QC); cross-validation rates were 81.67% (GA), 81.11% (SNN), and 86.11% (QC). The accuracy rates of the blinded validation test were 78% (GA), 84% (SNN), and 84% (QC). From the 27 discriminatory peptide peaks analyzed, 3 peaks of m/z 2860.34, 2881.54, and 3155.67 were identified as a fragment of fibrinogen alpha chain, fibrinogen beta chain, and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), respectively.Conclusions: Our results demonstrated that MS technique can be helpful in differentiation of benign and malignant liver tumors. Fibrinogen and ITIH4 might be used as biomarkers for the diagnosis of malignant liver tumors.

Introduction: There have been many inconsistent reports about the performance of histidine-rich protein 2 (HRP2) and lactate dehydrogenase (LDH) antigens as rapid diagnostic tests (RDTs) for the diagnosis of past Plasmodium falciparum infections.This meta-analysis was performed to determine the performance of pfHRP2 versus pLDH antigen RDTs in the detection of P. falciparum.Material and methods: After a systematic review of related studies, Meta-DiSc 1.4 software was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR).Forest plots and summary receiver operating characteristic curve (SROC) analysis were used to summarize the overall test performance.Results: Fourteen studies which met the inclusion criteria were included in the meta-analysis.The summary performances for pfHRP2-and pLDH-based tests in the diagnosis of P. falciparum infections were as follows: pooled sensitivity, 96.3% (95.8-96.7%) vs. 82.6%(81.7-83.5%);specificity, 86.1% (85.3-86.8%) vs. 95.9%(95.4-96.3%);diagnostic odds ratio (DOR), 243.31 (97.679-606.08)vs. 230.59(114.98-462.42);and area under ROCs, 0.9822 versus 0.9849 (all p < 0.001).Conclusions: The two RDTs performed satisfactorily for the diagnosis of P. falciparum, but the pLDH tests had higher specificity, whereas the pfHRP2 tests had better sensitivity.The pfHRP2 tests had slightly greater accuracy compared to the pLDH tests.A combination of both antigens might be a more reliable approach for the diagnosis of malaria.

目的 研究姜黄提取物对高脂饮食和CCL4联合致大鼠脂肪性肝炎治疗作用及初步机制研究.方法 60只SD雄性大鼠随机分为6组:正常组、模型组、阳性药组、姜黄低剂量组、中剂量组和高剂量组,模型组饲喂高脂饲料,并且腹腔注射CCL4(oil∶CCL4=50∶50);治疗组分别给予姜黄提取物低剂量50 mg/kg,中剂量100 mg/kg,高剂量200 mg/kg,阳性药组给予复方蛋氨酸胆碱片(东宝肝泰)162 mg/kg.给药6周后取动物血清,酶标仪法检测血清中谷丙转氨酶(ALT),谷草转氨酶(AST),甘油三酯(TG),胆固醇(TC),高密度脂蛋白(HDL),低密度脂蛋白(LDL)及肝组织中羟脯氨酸(Hyp);部分肝组织石蜡包埋后做HE、Masson染色,显微镜下观察肝组织病理切片;酶联免疫法检测白细胞介素6(IL-6),高迁移率族蛋白1(HMGB1);RT-PCR检测PPAR-γ,做组织PPAR-γ免疫组化病理检查.结果 治疗组与模型组相比,ALT,AST,Hyp,IL-6,HMGB1水平显著降低(P＜0.05),PPAR-γ表达增加.结论 姜黄提取物可治疗由高脂饮食联合CCL4致大鼠脂肪性肝炎,治疗作用机制主要可能是通过调控PPAR-γ信号通路,促进脂质代谢;另一方面通过降低IL-6、HMGB1的表达来减轻炎症,缓解肝纤维化,从而治疗非酒精性脂肪性肝炎.

目的 探究HIV初筛试验与确证试验的结果之间的关系,通过随访研究确证试验不确定结果的抗体进展情况.方法 2014年1月-2016年8月解放军302医院HIV抗体初筛阳性的地方患者331例,初筛方法为化学发光法,以免疫印迹法(Westem blotting,WB)作为确证试验,分析结果.并对不确定患者进行随访,分析其出现的条带,对转阳以及转阴的结果汇总统计.结果 初筛S/CO值在1～5之间的有84例,阳性符合率为0.00％,5～20之间的有36例,阻性符合率为22.22％,20～100之间的有65例,阳性符合率为67.69％,大于100的有146例,阳性符合率为98.63％.免疫印迹法检测后,72例不确定结果中存在多种条带,终判定为阳性的病人有13例,判定为阴性的病人为38例,失访21例.结论 化学发光试剂存在有一定的假阳性,随着S/CO值的升高,其与确证试验的阳性符合率也会升高,但是高S/CO值的标本并不一定代表感染了HIV.同时免疫印迹法检测HIV也有一定的局限性,所以建议HIV抗体的报告应该用初筛试验、复检试验、确证试验的结果进行综合判断.

Objective To identity microRNA (miRNA) diagnostic markers for chronic hepatitis B (CHB) and analyze the potential correlation between miRNA expression level and hepatitis B virus (HBV) replication.Methods We analyzed the expression level of 10 miRNAs in plasma samples from 50 CHB patients and 50 healthy Donors by Fluorescence quantitative PCR.A miRNA expression panel for chronic hepatitis B was found out through analysis of expression differences,accordingly a regression diagnosis model was established.The relationship between the miRNAs expression level and HBV DNA viral load was also visualized by Spearman rank correlation analysis.Results The expression level of 8 miRNAs were significantly different between CHB patients and healthy controls.miR-451 a was down-regulated and other 7 miRNAs were up-regulated.Logistic model based on data from miR-122-5p,miR-27a-3p and miR-451a showed that area under curve (AUC) was 1,and sensitivity and specificity of the diagnostics CHB from healthy sample reached 100％ in these case.The expression level of miR-122-5p had a significantly positive correlation with HBV DNA load.Conclusions For diagnosis of CHB,miR-122-5p,miR-27a-3p and miR451a could be used as new markers which play an important role in occurrence and development of CHB.

Objective: To investigate the diagnostic values of serum markers in liver fibrosis stages of chronic hepatitis B. Methods: The concentrations of TIMP-1, TIMP-2, AdipoQ, Leptin, PDGF and OPN in serum of 175 CHB patients were detected by means of ELISA and the relationships between the serum levels of markers and the liver fibrosis stages were analyzed by ROC curve. Results: There were statistically significant differences about the levels of TIMP-1, TIMP-2 and Leptin in serum of patients on different liver fibrosis stages(P0.05), and the AUROCs were higher than others. The other three markers had no statistically significant differences(P0.05). Conclusion: TIMP-1, TIMP-2 and Leptin had some diagnostic values in liver fibrosis stages of CHB patients. It is better to be detected with other markers in serum for the diagnostic of liver fibrosis.

Objective To construct and evaluate an artificial neural network (ANN) model as a new non-invasive diagnostic method for clinical assessment of liver fibrosis at early stage. Methods The model was set up and tested among 683 chronic hepatitis B (CHB) patients, with authentic positive clinical biopsy results, proved to have liver fibrosis or cirrhosis, admitted to 302 Hospital of PLA from May 2008 to March 2011. Among 683 samples, 504 samples were diagnosed as cirrhosis as a result of CHB, and 179 liver fibrosis due to other liver diseases. 134 out of 683 patients were included in training group by stratified sampling, and the others for verification. Six items (age, AST, PTS, PLT, GGT and DBil) were selected as input layer indexes to set up the model for evaluation. Results The ANN model for diagnosis of liver fibrosis was set up. The diagnostic accuracy was 77.4%, sensitivity was 76.8%, and specificity was 77.8%. Its Kappa concordance tests showed the diagnosis result of the model was consistent with biopsy result (Kappa index=0.534). The accuracy, sensitivity and specificity of CHB patients were 80.4%, 79.9% and 80.7% (Kappa index=0.598) respectively, and those for other liver diseases were 67.9%, 64.3% and 69.7% (Kappa index=0.316). Conclusion The artificial neural network model established by the authors demonstrates its high sensitivity and specificity as a new non-invasive diagnostic method for liver fibrosis induced by HBV infection. However, it shows limited diagnostic reliability to fibrosis as a result of other liver diseases.

Objective To monitor the constitutes and resistant tendency of diarrhea bacteria group and species in diarrheal patients in our hospital from 2002 to 2011 to offer the data for guiding epidemiologic study,vaccination research and clinical treatment.Methods We had cultured by SS agar and identified diarrhea bacteria to group and species with the biochemical and serologic test.Then we tested the susceptibility of diarrhea bacteria to 12 kinds antimicrobial agents.Results2352 isolates including Salmonella,Shigella,Vibrio,Aeromonas,diarrheagenic Escherichia coli.Which caused diarrhea were identified during 10 years.Among them,Shigella was the most and occupied 52.90%.With the time changing,there was changing of distribution from 2007,Shigella had reduced to 32.80%and Salmonella and Escherichia coli diarrheogenic had increased from 4.90%and 3.60%to 15.40%and 19.70%respectively.The higher resistant rate of diarrhea bacteria happen to ampicillin(75%-85%) and Trimethoprim-sulfamethoxazole(51%~66%).The resistant rateof diarrhea bacteria toBroad-spectrum penicillins,fluoroquinolones and cephalosporins was increased obviously during 10 years.Furthermore,multiple antibiotic resistant strains was increased from 24.67%to29.01%.Conclusions There was many kinds of diarrhea bacterial caused diarrhea in local area and different drug resistant rate to different antibiotics.Resistant and Multiple resistant-drug bacteria was increasing during research time.It is necessary to supervise for prevention and treatment.