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Posttransplant lymphoproliferative disease (PTLD) is a series of heterogeneous lymphoproliferative diseases and a severe complication after solid organ transplantation in children. Over 70% of PTLD is associated with Epstein-Barr virus (EBV). EBV-related B-cell lymphoma is also the main malignant tumor after pediatric organ transplantation. EBV-related PTLD is still a challenge in pediatric solid organ transplantation, which is mainly caused by immune function damage induced by immune suppression after transplantation. However, the specific mechanism remains elusive. In recent years, biomarkers have been developed to guide the diagnosis and individualized treatment of EBV-related PTLD, which possesses excellent application prospect. In this article, research progresses on the incidence of EBV-related PTLD in solid organ transplantation and its biomarkers were reviewed, aiming to explore novel ideas for clinical diagnosis and treatment.
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Epstein-Barr ( EB) virus is wildly spreaded in human and associated with many diseases. EBV-DNA load measurement by PCR has been shown to play an important role in the diagnosis of these disea-ses, a method to monitor patients and a prognosis factor of the outcome in many EBV-associated diseases. This review focuses on the development of the EBV-DNA detection technique and the advances of clinical use in sev-eral non-neoplastic EBV-associated diseases in children.
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To study the effect and underlying mechanism of Mahuang Tang against influenza A virus ， the influenza virus-infected Madin-Darby canine kidney(MDCK) cells were used as the carrier in this study to detect the median tissue culture-infective dose(TCID₅₀) of influenza A virus strains(A/PR8/34) on MDCK cells with cytopathic effect(CPE) assay. Blocking influenza virus invading host cells and anti-influenza virus biosynthesis were used as two different administration methods， and then the methyl thiazolyl tetrazolium(MTT) assay was utilized to determine the antiviral effective rate(ER)， median efficacious concentration(EC₅₀) and therapeutic index(TI) of Mahuang Tang. The quantitative Real-time polymerase chain reaction(RT-PCR) was used to measure virus load and the mRNA expression levels of TLR4， TLR7， MyD88 and TRAF6 in MDCK cells at 24， 48 h after the treatment. The experiment results indicated that TCID₅₀ of A/PR8/34 for MDCK cells was 1×10-4.32/mL. The EC₅₀ values of two different treatment methods were 4.92，1.59 g·L⁻¹ respectively， the TI values were 12.53， 38.78 respectively， and when the concentration of Mahuang Tang was 5.00 g·L⁻¹， ER values were 50.21%， 98.41% respectively， showing that Mahuang Tang can block influenza virus into the host cells and significantly inhibit their biosynthesis. Meanwhile， as compared with the virus group， the virus load was significantly inhibited in Mahuang Tang groups， and Mahuang Tang high and middle doses had the significant effect on decreasing the mRNA expression of TLR4， TLR7，MyD88 and TRAF6 at 24， 48 h after the treatment. It can be demonstrated that the mechanisms of Mahuang Tang against influenza A virus are related to the inhibition of influenza virus replication and the mRNA expression of correlative genes in TLR4 and TLR7 signaling pathways.
Subject(s)
Animals , Dogs , Antiviral Agents , Pharmacology , Drugs, Chinese Herbal , Pharmacology , Influenza A Virus, H1N1 Subtype , Physiology , Madin Darby Canine Kidney Cells , Orthomyxoviridae Infections , Toll-Like Receptor 4 , Metabolism , Toll-Like Receptor 7 , Metabolism , Virus ReplicationABSTRACT
Objective To evaluate the effects of hepatitis B virus on liver function,liver fibrosis,and liver pathological staging at different immune stages.Methods We made a retrospective analysis of 657 patients with chronic hepatitis B diagnosed in the First Hospital of Lanzhou University.Their liver function parameters,liver fibrosis parameters,and hepatitis B virus load were measured by automatic biochemical analyzer,automatic gammaradiation immunity analyzer,and quantitative PCR analyzer,respectively.Effects of hepatitis B virus on liver function,liver fibrosis in different immune stages were analyzed by variance analysis.Effects of hepatitis B virus on liver pathological staging at different immune stages were analyzed by linear trend chi square test analysis.Results In ALT normal chronic hepatitis B patients group,viral load had mild effects on liver function and liver fibrosis parameters.However,in ALT abnormal chronic hepatitis B patients group,viral load had a significant effect on liver function and liver fibrosis parameters,and the effect was most obvious in ALT＞double upper limit of normal group.The specific manifestation was that with viral load increasing,liver function parameters including ALT,AST,TBiL,DBiL,and IBiL increased,while TP and ALB decreased.Liver fibrosis parameters HA,LN,PcⅢ,and CIV all increased (P＜0.05).In ALT normal chronic hepatitis B patients group,viral load had no relationship with liver pathological staging.However,in ALT abnormal chronic hepatitis B patients group,especially ALT≥double upper limit of normal group,viral load was significantly related to liver pathological staging.Conclusion The effects of hepatitis B virus on patients' liver function at different immune stages were different,thus providing evidence-based medicine support for clinical antiviral treatment.
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Objective:To evaluate high-risk human papillomavirus (hrHPV) genotyping and viral load in predicting CIN (cervical intraepi-thelial neoplasia (CIN) grade 2 or worse in a Chinese rural area population with limited health resources. Methods:We performed a population-based prospective study and enrolled 2,257 women aged 35 to 64 years from three rural screening sites of Jiangxi prov-ince. We conducted a hybrid capture (HC-2) assay to predict viral load. A HC-2 relative light unit (RLU) threshold of 10 was set to differ-entiate samples between low (<10) and high (≥10) viral loads. We also carried out a HybriMax test to detect different hrHPV geno-types in the samples. Women exhibiting positive HC-2 or HybriMax results underwent colposcopy and colposcopically directed biopsy. Women with negative or positive hrHPV test results but with normal biopsy or CIN1 were followed-up for 24 months without interven-tion (n=2,211). We used histopathological findings as outcome. Results:Of the 2,211 women, 1,636 provided complete follow-up data. Of the 132 women with a high viral load, 4 (3.03%) developed CIN2+in the same period. The relative risk (RR) of CIN2+for HC-2 posi-tivity at baseline was 42.24 (95%CI=4.76-375.2). Of the 159 women who were positive for HPV16 or HPV18 upon screening, 4 (2.52%) progressed to CIN2+(RR=33.06, 95%CI=3.72-293.9). The 2-year cumulative incidence rates of CIN2+did not significantly differ be-tween the high viral load group and the HPV16/18 group. Conclusion:The risks of CIN2+progression were higher among women with a high viral load or HPV16/18 positivity than among women with negative hrHPV. Increasing the HC-2 cut-off value to 10 RLU or using HPV16/18 positivity may be similarly used to triage hrHPV-positive women for immediate colposcopy and comprehensive follow-up.Both approaches were equally predictive of the CIN2+risk in rural area. Increasing the HC-2 cut-off value to 10 RLU may also help allo-cate health resources effectively.
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Objective It's not clear why the severity of hand-foot-mouth disease (HFMD) caused by enterovirus 71 (EV71) was varied clinically.In this study,the relation between the virus load of EV71 and the severity of HFMD was analyzed and the foundation for HFMD control and treatment were laid.Methods Two hundred and fortyseven patients with HFMD caused by EV71 from Jan.2012 to Sep.2013 in Xi'an Children's Hospital were enrolled and clinical data were collected,including age,gender,clinical symptoms,signs,routine blood count,fasting glucose,C-reactive protein and enterovirus.The EV71 virus loads of 247 patients with HFMD were measured by real-time PCR assay.Meanwhile,the effect of EV71 RNA on the severity of HFMD was analyzed.Results In this study,121 mild cases and 126 severe cases with HFMD limb shaking,fasting glucose,lymphocyte and neutrophil percentage were statistically significant between the 2 groups (all P ＜ 0.05).The counts of EV71 RNA from all of the 247 throat swab samples were more than 100 copies/mL,and the highest virus load was 1.1 × 105 copies/mL.The highest value of EV71 RNA was 9.32 × 104 copies/mL and 1.1 × 105 copies/mL in mild and severe cases,respectively,there was no significant difference between the 2 groups (P ＞ 0.05).Conclusions The results of EV71 RNA by RT-PCR are visualized and convenient.The virus loads of EV71 are not associated with the severity of HFMD,but further studies need to analyze.
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Objective To explore the relationship between HBV-DNA load and the offspring vertical transmission of HBV.Methods 138 families who had taken the examination between August 2009 and November 2011 but the HBsAg of the housewife was negative,were chosen as research objects.Blood from the couples and sperms from the husbands during pregnancy were followed and collected for detection on related indicators.Cord blood was sampled after delivery for HBVM and HBV-DNA quantification.Those with HBV-DNA load ≥5 × 102 copies/ml were chosen as cases while those ＜5 × 102 copies/ml were formed as controls,respectively.Results 1) The positive rates of HBV-DNA was 34.8％ (48/138) in the neonatal cord blood while the positive rates of cord blood HBsAg and HBeAg were 28.3％ (39/138) and 15.2％ (21/138) respectively.2) The positive rate of semen HBV-DNA was 21.0％ (29/138) while the positive rates of paternal serum HBV-DNA and HBeAg were 76.8％ (106/138)and 42.8％ (59/138).3)Among the positive ones on paternal serum HBV-DNA,paternal serum HBeAg,semen HBV-DNA,items as measures taken for HBV vertical transmission and prevention on the fathers and the first class family histories on HBV appeared to be the risk factors for HBV paternal transmission (P＜0.05).4)Data from Multivariate analysis showed that positivities on patemal serum HBV-DNA,paternal serum HBeAg and semen HBV-DNA were risk factors for HBV paternal transmission (OR=5.7,95％CI:1.1-29.1 ; OR=4.2,95％CI:1.7-10.0; OR=6.7,95％ CI:2.4-18.9).5)Dose-response relationships were seen between levels of paternal serum HBV-DNA load and cord blood HBV-DNA load,between levels of paternal serum HBV-DNA load and semen HBV-DNA load,between levels of semen HBV-DNA load and cord blood HBV-DNA load.6)Results from the analysis on ROC curve showed that paternal serum HBV-DNA load level (105 copies/ml) and semen HBV-DNA load level (103 copies/ml)were better demarcation points to forecast the occurrence of paternal transmission of HBV,because of the better sensitivity and specificity they had.Conclusion Items as positives on paternal serum HBV-DNA,paternal serum HBeAg and semen HBV-DNA were risk factors for HBV paternal transmission.When paternal serum HBV-DNA load ＞ 105 copies/ml and semen HBV-DNA load ＞ 103 copies/ml appeared,the positive rate of HBV paternal transmission would increase.
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Objective To analyze the CD4 +T cells and virus load in HIV/AIDS affected population and to evaluate the HIV/AIDS antiretroviral therapy programs in Henan province.Methods "Henan HIV/AIDS Testing Laboratory Network Database" was used to collect the data on CD4+ T cells and virus load (VL) value and corresponding information in HIV/AIDS population of Henan in 2009. Cross-sectional studies was used to study the constituent ratio of CD4 + T cells and virus load value in individuals who had not received antiretroviral-treated (ART) and had joined first-line ART between the year of 2005 to 2008 among HIV/AIDS population of Henan. Results As to these people living with HIV/AIDS that had not received ART in the first half and the second half year of 2009, the constituent ratio of individuals whose CD4+T cells were less than 200 cells/μl both accounted for more than 20% (χ2=2.059, P=0.151). The constituent ratio of individuals whose CD4+T cells were in 200-350 cells/μl and more than 350 cells/μl increased from 27.61% to 29.41%(χ2=4.636, P=0.031 ) and decreased from 51.49% to 48.60% (χ2=9.767, P=0.002), respectively.Meanwhile, we saw 34.53% and 19.65% of the patients whose virus load was ＞10 000 copy/mland ＞30 000 copy/ml in this population. Patients that joined first-line ART during 2005-2008 showed the following results: the longer of the therapy time, the higher constituent ratio of individuals whose CD4+ T cells were more than 350 cells/μl (χ2= 148.689, P＜0.001) and the lower constituent ratio of individuals of whose CD4+T cells were less than 200 cells/μl (χ2=46.686,P＜0.001).Simultaneously, the lower constituent ratio of individuals whose viral load was less than 500 copy/ml (χ2=9.066, P=0.003) and the higher constituent ratio of individuals whose virus load was more than 10 000 copy/ml (χ2=6.597, P=0.010). Conclusion Significant curative effect had been achieved in AIDS first-line ART of Henan, but along with the increasing treatment time, the risk of treatment failure also increased. Drug resistance test and changing of treatment protocols were needed. To reach better and more efficient effects on therapy, factors as more detections and investments on ART, expanding the scope of treatment etc. were needed on those people living with HIV/AIDS that had not received ART.