1.Analysis of peripheral blood lymphocyte subsets and its correlation with the rapid plasma reagin titers in serofast syphilis patients
Qipeng XIE ; Chao XING ; Qiong ZHANG ; Jian YU ; Huaikai WEN
Chinese Journal of Infectious Diseases 2017;35(3):165-168
Objective To investigate the reason of persisting positive rapid plasma reagin (RPR) in serofast syphilis patients, and to provide reference for clinical treatment and prognosis.Methods A total of 33 serofast patients and 23 healthy controls were enrolled in this study.The percentages and absolute counts of CD3+, CD4+, CD8+ T lymphocytes and natural killer (NK) cells were detected by flow cytometry.The comparison of two groups was analyzed by independent sample t test, and the correlation between change of lymphocyte subgroups and RPR titer in serofast syphilis patients was analyzed by bivariate linear correlation method.Results Compared with healthy controls, the percentages of CD3+, CD8+ T lymphocytes in serofast syphilis group were both increased significantly (75.75±5.76)% vs (68.37±5.80)%, (t=4.69, P<0.01);(27.34±7.02)% vs (24.33±1.95)%, (t=2.34, P=0.025), while both the percentage and absolute count of NK cells were significantly decreased (7.32±4.48)% vs (14.87±6.26)%, (t=5.269, P<0.01);(136.2±83.4)/μL vs (298.8±166.9)/μL, (t=4.311, P<0.01).RPR titer of the patients was negatively correlated with both percentage and absolute count of CD4+ T lymphocytes (r=-0.476 and-0.515, respectively, both P<0.01), and it was positively correlated of CD8+ lymphocytes (r=0.588 and 0.305, P<0.01 and P=0.804).Conclusion The imbalance of immune response of lymphocyte subsets observed in serofast syphilis may explain the RPR titers change.
2.The therapeutic effect and its mechanism of dendritic cells overexpressed suppressors of cytokine signaling 1 on acute liver failure in mice
Shengguo ZHANG ; Shanshan LI ; Xinyue TANG ; Min YANG ; Mingqin LU
Chinese Journal of Infectious Diseases 2017;35(3):151-156
Objective To investigate the impact of suppressor of cytokine signaling 1 (SOCS1) overexpression on dendritic cells (DC) functions and its therapeutic effect on acute liver failure (ALF) in mice.Methods Bone marrow derived dendritic cells (BMDC) from C57BL/6 mice were transfected with lentivirus encoding SOCS1 and negative control lentivirus at a MOI=50, and labeled as DC-SOCS1and DC-VNG, respectively after 96 hours of successful transduction.Then DCs were stimulated with lipopolysaccharides(LPS)1 mg/L and collected for flow cytometry analysis of surface costimulatory molecules, allogeneic mixed lymphocyte reaction (MLR) and western blot test of Janus kinase (JAK)/signaling transducers and activators of transcription (STAT) pathway.Afterwards, 90 mice were randomly assigned into 4 groups including 12 in normal control group, 26 in ALF group, 26 in treatment groups with DC-SOCS1 and 26 with the treatment of DC-VNG.All were received tail vein injection with normal saline, modified DC-VNG and DC-SOCS1 suspended in normal saline, respectively.Twelve hours after injection, LPS (10 μg/kg)/D-GaIN (600 mg/kg) were injected intraperitoneally to induce ALF model.The mortality, serum levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), liver pathology and proportion of splenic regulatory T cells of each group were observed.Means in different groups were compared with one-way ANOVA analysis.Categorical variables were analyzed with x2 test.Variables were examined with normality test and homogeneity of variance with LSD test.Results The results of mixed lymphocyte reaction (MLR) revealed that T cell proliferation ratio in DC-SOCS1 group with mixture ratio of 100∶1 were (25.87±0.38)%, which was lower than that of mixture ratio of 10∶1 in the mDC group ([84.29±3.25]%) with statistical significance (x2=49.821, P<0.01);interleukin (IL)-10 concentration was higher than that in mDC group with mixture ratio of 10∶1 with statistical significance (F=20.112, P<0.05);IL-6 concentration was also lower with statistical significance (F=47.718, P<0.05).Compared to imDC, expression of JAK2 (t=0.525,0.523 and 0.489, respectively, all P<0.01), signal transduction factors and activation of transcription factors-1 (STAT1) (t=0.442,0.400 and 0.402, respectively, all P<0.01) and SOCS1 (t=0.322,0.363 and 1.090, respectively, all P<0.01) of mDC, DC-VNG and DC-SOCS1 after LPS stimulation increased significantly.Furthermore, the expressions of phosphorylated STAT1 (p-STAT1) and phosphorylated JAK2 (p-JAK2) of DC-SOCS1 were much lower than those of the mDC, with statistically significant difference (t=-3.840 and 0.254, respectively, both P<0.01).Pathological analysis revealed that there existed moderate hepatic cells necrosis and less immune cell infiltration in DC-SOCS1 group accompanied with higher regulatory T lymphocytes proportion than those in ALF group and DC-VNG group.Survival rate of ALF with DC-SOCS1 treatment group was significantly higher than that of ALF group with statistical difference (x2=12.87, P<0.05).Conclusions DC-SOCS1could sustain an immature state and exhibit as regulatory DC through negative regulation of JAK2/STAT1 pathway with overexpression of SOCS1.Infusion of DC-SOCS1 could ameliorate ALF by inhibiting aggressive inflammation response with increased proportion of regulatory T cells in mice, which shows good therapeutic effect for ALF mice.
3.Clinical characteristics of 113 brucellosis with liver injury
Bin JIA ; Xinhua BAI ; Lijun CHEN ; Yuexin ZHANG
Chinese Journal of Infectious Diseases 2017;35(3):138-141
Objective To summarize the characteristics of liver injury due to brucellosis to provide reference for clinical diagnosis and treatment of brucellosis.Methods A total of 359 patients with brucellosis at the First affiliated Hospital of Xinjiang Medical University during 2010-2016 were enrolled, among them 113 (31.5%) developed liver injury.Alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyl transferase (γ-GT), serum albumin (Alb), alkaline phosphatase (ALP) and total bilirubin (TBil) were obtained before and after treatment.Ultrasound of upper abdomen was performed to observe the morphological changes of liver and spleen at admission.The routine blood test, erythrocyte sedimentation rate, C-reactive protein and other laboratory examinations were also performed.The data of patients before and after therapy were analyzed by t test.Results A total of 113 patients were included in this study.Eighty-eight (77.9%) were male.The mean age was (43.2±15.8) years old, among whom 81(71.7%) cases were between 31 and 60 years old.Seventy-one cases (62.8%) was in acute phase, and 42(37.2%) in chronic phase.The Han, Uighurs and Kazak nationalities accounted for 41.6%(47 patients),31.0%(35 patients) and 18.6%(21 cases), respectively.At admission, ALT level was (98.54±59.32) U/L before treatment, and decreased to (38.18±17.13) U/L after treatment, with statistically significant difference (t=6.627, P<0.05).AST levels before and after treatment were (93.17±59.19) U/L and (30.67±12.56) U/L, respectively, with significant difference (t=8.042, P<0.05).γ-GT levels before and after treatment were (162.27±48.19) U/L and (69.53±32.17) U/L, respectively, with statistically significant difference (t=8.271, P<0.05).Alb was (32.31±5.29) g/L before therapy, and increased to (38.00±4.27) g/L after therapy, with statistically significant difference (t=4.429, P<0.05).Conclusions Liver injury is common in patients with brucellosis.Elevation of transaminase is usually mild to moderate, accompanied by reduced ALB.For brucellosis patients with liver injury, antimicrobial treatment combined with liver protecting drugs could improve liver function effectively, and even within the normal range.
4.Clinical features of 82 patients with brucellosis in Liaoning Province
Shengli JIANG ; Yulan BAI ; Baiyi CHEN
Chinese Journal of Infectious Diseases 2017;35(3):134-137
Objective To identify the clinical features of patients with brucellosis in Liaoning Province in recent 5 years, and to improve the diagnostic level of the disease.Methods The clinical data including epidemiology, clinical features, laboratory data and diagnosis of 82 hospitalized patients who were diagnosed with brucellosis in the First Affiliated Hospital of China Medical University from 2011 to 2015 were collected and reviewed retrospectively.Results The majority of the 82 patients were middle-aged (45-59 years old) (47.6%) and male gender (63.4%).Fever (90.2%), muscle and joint pain (61.0%), hepatosplenomegaly (36.6%), lymphadenopathy (24.4%) and weight lose (32.9%) were the main complaints.The peripheral leucocyte counts were usually normal (70.7%).C-reactive protein (81.3%), procalcitonin (81.8%) and erythrocyte sedimentation rate (64.2%) increased in most cases.The results of the serum agglutination test in 67 patients were all positive (100.0%).The pathogen isolation was conducted in 60 patients and 49 patients were positive for Brucella species.Among them, 35(71.3%) isolates were identified as Brucella melitensis.A total of 90.2%(74/82) cases were firstly diagnosed with fever of unknown origin and were hospitalized.Misdiagnosis accounted for 52.4(43/82)%.Conclusions Contact history with cow and sheep should be inquired thoroughly in patients with clinical manifestations of fever, muscle and joint pain and hepatosplenomegaly.Pathogen isolation, agglutination test and other specific tests should be performed as soon as possible to diagnose the disease early.
5.Expression of microRNA-3620 in blood plasma and its clinical significance in patients with anti-tuberculosis drug-induced hepatotoxicity
Ping XIE ; Tong ZHU ; Caiping CHEN ; Ru BAI ; Hui ZHAO ; Weixing ZHU ; Liangming LIU
Chinese Journal of Infectious Diseases 2017;35(3):161-164
Objective To investigate the expression of microRNA (miRNA)-3620 in the plasma of patients with anti-tuberculosis drug-induced hepatotoxicity (ATDH).Methods A total of 35 patients with ATDH and 35 non-ATDH paired individuals were included in this study.Plasma miRNA-3620 levels were detected using real-time Polymerase chain reaction.Comparison between two groups was done with t test.Receiver operation characteristic (ROC) curve analysis was performed to determine the diagnostic value of miRNA-3620 in ATDH.Results The relative expression of plasma miRNA-3620 of patients with ATDH and non-ATDH were 1.65±1.43 and 0.71±0.45, respectively, with significantly statistical difference (t=3.703, P<0.01).The cut off value of miRNA-3620 expression was 1.15 and the area under ROC curve were 0.71(95% CI: 0.43-1.45).Based on this cutoff value, the sensitivity and specificity of miRNA-3620 in diagnosing ATDH were 60.0% and 82.9%, respectively;the positive predictive value was 77.8% and the negative predictive value was 67.4%.Twenty-one ATDH cases and 29 non-ATDH cases was correctly diagnosed, with the accuracy of 71.4%.Conclusion The expression of miRNA-3620 in plasma is significantly increased in ATDH patients.
6.Diagnostic value of serum Mp1p antigen detection for Talaromyces marneffei infection in acquired immune deficiency syndrome patients
Linghua LI ; Saiyin XIAO ; Yan HE ; Fengyu HU ; Wanshan CHEN ; Huali LEI ; Xiaoping TANG ; Weiping CAI
Chinese Journal of Infectious Diseases 2017;35(3):157-160
Objective To explore the diagnostic value of Talaromyces marneffei (T.marneffei)-specific mannose glycoprotein Mp1p antigen for T.marneffei infection in acquired immune deficiency syndrome (AIDS) patients.Methods All cases were recruited in this study from January 2012 to June 2015 in Guangzhou No.8 People′s Hospital, including 184 AIDS patients with T.marneffei infection confirmatively diagnosed by culture, and 205 controls including 176 AIDS patients without T.marneffei infection and 29 health controls.Double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were both utilized to detect serum Mp1p antigen levels, and their sensitivity and specificity for diagnosing T.marneffei infection in patients with AIDS were analyzed.x2 test and t test were used for statistical analysis.Results The ratio of males to females and age of the study group were both comparable to those of the control group (x2=0.019, P=0.889;t=1.810,P=0.07, respecitvley).The sensitivities of double antibody sandwich enzyme linked immunosorbent assay and fluoroimmunoassay combined with double-antibody sandwich were 82.07%(151/184) and 83.15%(153/184), respectively (x2=0.076, P=0.783).The specificities were 93.17%(191/205) and 92.68%(190/205), respectively (x2=0.037, P=0.847).The accuracy values were 87.92%(342/389) and 88.17%(343/389), respectively (x2=0.012, P=0.912).The false positive rates were 6.83%(14/205) and 7.32%(15/205), respectively.The false negative rates were 17.93%(33/184) and 16.85%(31/184), respectively (x2=0.049, P=0.829).The positive predictive values were 91.52%(151/165) and 91.07%(153/168), respectively (x2=0.021, P=0.886).The negative predictive values were 85.27%(191/224) and 85.97%(190/221), respectively (x2=0.045, P=0.832).The Kappa values were 0.83 and 0.80, respectively.Conclusion Detection of serum Mp1p antigen of T.marneffei possesses high specificity and sensitivity, which may be utilized for rapid and early diagnosis of T.marneffei infection in patients with AIDS.
7.Laboratory investigation of reactive plasmacytosis in patients with severe fever with throbocytopenia syndrome
Rui ZHENG ; Meizhen DAI ; Qing WANG ; Huazhong CHEN ; Huijun LIN ; Baoguo CHEN ; Boli LI
Chinese Journal of Infectious Diseases 2017;35(3):146-150
Objective To investigate the immunological characteristics and clinical significance of reactive plasmacytosis in patients with severe fever with throbocytopenia syndrome (SFTS).Methods Bunyavirus-infected patients who were diagnosed with SFTS were collected from March 2015 to October 2015 in Taizhou Hospital.Morphology analysis of bone marrow and peripheral blood (PB) smear, as well as flow cytometry analysis of plasma cell immune phenotype from peripheral blood were conducted.Serum immunoglobulin levels and helper T hymphocytes (Th)1/Th2 cytokine expressions were detected.Mann-Whitney U test was used.Results PB plasma cells from all of the SFTS patients increased in varying degrees, and the phenotype of the plasma cells was CD19+CD38++CD45+CD138+, which indicated normal mature plasma cells.The ratio of PB plasma cells was >0.030 in 10/16 patients, and >0.300 in 2/16 patients.The ratios of PB plasma cells in the patients with severe and critical groups were significantly higher than that in the mild group (0.052 vs 0.016, P<0.05).Monocytoid histiocytes and hemophagocytes were observed in the BM morphology of 9 patients.Three of them were diagnosed as hemophagocytic lymphohistiocytosis (HLH).The ratio of plasma cells was more than 0.030 in the bone marrow of 8 patients.The serum levels of interlewkin (IL)-6, IL-10 and interferon (IFN)-γ in acute phase were significantly elevated with the median level of 49.75 ng/L, 26.98 ng/L (reference value 2.6 to 4.9 ng/L) and 17.57 ng/L, respectively.While the levels of IL-2, IL-4 and twmor necrosis fautor(TNF)-α were not significantly changed.The serum IL-6 and IL-10 levels in the patients with severe and critical groups were both significantly higher than those in the mild group (IL-6: 132.36 vs 22.81 ng/L;IL-10: 75.28 vs 6.33 ng/L, both P<0.05), but the difference of IFN-γ level was not significant (P>0.05).The serum IgG, IgA and IgM levels did not increase in acute stage, with the median of 11.6 g/L, 2.56 g/L and 1.60 g/L (reference value 0.46 to 3.04 g/L), respectively.Conclusion The patients with SFTS show excessive humoral and cellular immunity, and the severity of disease is positively correlated with the ratio of peripheral plasma cells and the levels of cytokines IL-6 and IL-10.
8.Pathogenic spectrum, clinical features and drug resistance of pneumonia caused by nontuberculous mycobacteria in acquined immunodeficiency syndrome patients
Yue WU ; Xizi DENG ; Fengyu HU ; Wanshan CHEN ; Xiejie CHEN ; Weiping CAI ; Xiaoping TAMG ; Linghua LI
Chinese Journal of Infectious Diseases 2017;35(3):142-145
Objective To explore the pathogen spectrum, drug resistance rate and clinical characteristics of pneumonia caused by non-tuberculous mycobacteria (NTM) in acquined immuno-deficiency syndrome (AIDS) patients.Methods The clinical data of 31 hospitalized AIDS patients with bronchoalceolar lavage flind (BALF) culture confirmed NTM pulmonary disease in Guangzhou No.8 People′s Hospital from January,2008 to February,2015 were retrospectively analyzed, including pathogen spectrum, drug resistance rate and clinical characteristics.The clinical characteristics and drug resistance were compared between Mycobacterium avmm-intracellulare complex (MAC) pneumonia and the non-MAC pneumonia, and t test and chi-square test were used.Results Of the 31 AIDS patients,28 were male and 3 were female, with the mean age of 40.9 years old.The 31 NTM strains were consisted of 14 MAC strains and 17 non-MAC strains (including 4 M.kansasii strains,3 M.lentiflavumstrains, 2 M.szulgai strains, 2 M.yongonense strains etc).There was no significant difference between two groups in sex ratio, mean age, clinical manifestations, laboratory tests and treatment outcome (all P>0.05).The major clinical manifestations included fever, productive cough, weight loss, anemia and low CD4+ count (<50/μL).Most patients showed thoracic lymphadenectasis and patchy shadows in lungs, and few patients had millet shadows and pericardial effusion.Compared with non-MAC strains, MAC strains had higher drug resistant rate of moxifloxacin (10/14 vs 4/17), levofloxacin (14/14 vs 8/17), and clarithromycin (11/14 vs 7/17).More extensively drug resistance strains were seen in non-MAC strains compared with MAC strains (11/14 vs 7/17).Conclusions MAC is the most common pathogen of NTM pulmonary disease in AIDS patients.The clinical features of pneumonia caused by MAC and non-MAC are similar, but drug resistance of MAC strains are more severe.
9.Impact of regulatory T-lymphocytes on therapeutic efficacy of human acute brucellosis
Feihuan HU ; Guoxia ZHANG ; Yanjun TIAN ; Lijie ZHANG ; Bailing LIU ; Wenjing WANG ; Chengyao LI
Chinese Journal of Infectious Diseases 2017;35(3):129-133
Objective To investigate the humoral and cellular immune responses in patients with acute brucellosis, and evaluate dynamic changes of regulatory T-lymphocytes (Foxp3+ Treg) in the peripheral blood of patients during treatment, in order to clarify the relationship between immunosuppression and the therapeutic effect in human brucellosis.Methods Sixty-five patients with brucellosis hospitalized at the Third Department of Infectious Diseases, Heilongjiang Agriculture and Reclamation Bureau General Hospital between July 2015 and November 2015 were included.Twenty-eight patients were treated with conventional therapy (group A: patients received 3 courses of treatment.Each lasted for 20 days with one-week interval), and 37 patients were treated with conventional therapy in combination with immunopotentiator (group B).Thirty healthy volunteers were enrolled as the controlled group.The ratio of CD3+CD4+ Foxp3+ Treg cells in the peripheral blood of brucellosis patients were measured by flow cytometry (FCM) at the end of each course of treatment.Data in accordance with normal distribution were described as mean±standard deviation.Comparison between two groups was done by two sample t test.Comparison among multiple groups was performed by analysis of variance and SNK test.Data that did not fit the normal distribution were analyzed by multiple-sample nonparametric test.Results After the first (20 d), second (50 d) and third course of treatment (80 d), the ratios of Foxp3+Treg in the peripheral blood of 65 acute brucellosis patients were 2.83%, 3.77% and 4.03%, respectively, which were all significantly higher than control group (1.69%;t=5.97, 9.05 and 5.66, respectively, all P<0.01).At the end of the first course of treatment, the ratios of Foxp3+Treg in group A and B showed no statistically difference (t=0.33, P>0.05), while those were both higher than control group (t=7.09 and 4.94, respectively;both P<0.01).At the end of the second course, the ratio of Foxp3+ Treg in group B was higher than group A (t=2.22, P<0.01), and both of them were higher than control group (t=10.79 and 7.25, respectively;both P<0.01).At the end of treatment, Foxp3+ Treg in group A was also significantly higher than the other two groups (t=6.02 and 6.45, respectively;both P<0.01).Conclusions In patients with acute brucellosis treated with the standard antibiosis treatment in combination with immunopotentiator, the ratio of Foxp3+Tregs significantly increases and maintains at a high level, which suggests that extra immunopotentiator may be not helpful for the treatment of brucellosis at the very early stage.
10.Alteration of surfactant protein A and D in bronchoalveolar lavage fluid in rats with pneumocystis carinii pneumonia
Jieming QU ; Zhaohui RONG ; Lixian HE
Chinese Journal of Infectious Diseases 2000;18(2):91-94,illust1
Objective To study the alteration of surfactant protein A and D(sp-A,SP-D)result-ing from pneumcystis carinil pneumonia(PCP)and investigate its implication in the pathogenesis of PCP.Methods SD rat models of PCP were induced by subcutaneous injection of 25 mg cortisone acetate,normal control and negative control as well as bacterial pneumonia group were set up for comparison.During 8~12weeks.broncboalveolar lavage fluid (BALF) of rats was collected.Total nucleate cells of BALF were counted and differentiated as well as the concentrations of surfactant protein A(SP-A)and surfactant pro-tein D(SP-D)were measured by immunoblotting assay.Results The rats were divided into three im-munosuppressive groups,plus a norrflal control group. Group A: normal control(n=6)consisted of healthy SD rats;group B:negative control(n=6)employed rats with cortisone acetate injection over 8weekz without tung infection;group C:bacterial pneumonia(n=11),rats were injected with cortisone ac-etate over 8 weeks and resulted in bacterial pneumonia without other pathogens isolated;group D(n=14):rats were injected with cortisone acetate during 8~12 weeks and resulted in PCP without other pathogens isolated.During PCP infection,the total cell counts and the percentage of polymorphonuclears (PMNs)in BALF were significantly increased(P<0.01),but were lower than those in the bacterial pneumonia group.The concentration of SP-A of BALF in PCP(45.1 μg/ml 4±22.1 μg/m1)was signifi-cantly increased in comparison with that in negative control group(16.2 μg/ml±9.9 gg/ml,P<0.05)and that in bacterial pneumonia group(6.2 μg/ml±5.6 μg/ml,P<0.001).We also found that the rela-tive content of SP-D was significantly higher in PCP(24 249±4 780 grey values)than that in both nega-tive control(13 384±2 887 grey values,P<0.001)and bacterial pneumonia group(11 989±2 750 grey values,P<0.001).SP-A and SP-D were also higher in moderate to severe group of PCP than those seen in mild group(P<0.01,P<0.001).Conclusion There was obvious increase of SP-A and SP-D in PCP rats,and particularly,the change of which was greater than that in bacterial pneumonia.Therefore,the alteration of SP-A and SP-D may be of implication in the prevention and management of PCP.