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Objective:To investigate the effects and significance of acute and chronic trauma on brain degree centrality (DC) in patients with post-traumatic stress disorder (PTSD) who lost their only child at resting state.Methods:Retrospectively, the study enrolled a total of 51 parents with PTSD, including 35 PTSD parents whose children was lost in emergencies (acute bereaved PTSD group) and 16 PTSD parents whose children was lost of chronic causes such as diseases (chronic bereaved PTSD group). Fifty local adults were also included as healthy controls (HC group). The clinical administered PTSD scale(CAPS) was used to evaluate the severity of the subjects' clinical symptoms.Resting-state functional magnetic resonance imaging(fMRI) data of all subjects were collected and DC values were calculated.SPSS 22.0 software was used for statistical analysis.Covariance analysis was performed among three groups, while post hoc was performed between any two groups.What's more, correlation analyses were utilized between abnormal brain regions and the scores of CAPS.Results:Significant group effects were found in multiple regions, including the right inferior temporal gyrus (MNI: x, y, z=66, -27, -21), right temporal pole (MNI: x, y, z=54, 15, -9), right orbital inferior frontal gyrus (MNI: x, y, z=42, 21, -15), bilateral medial superior frontal gyri (MNI: right x, y, z=6, 63, 12; left x, y, z=-3, 60, 18), left inferior parietal angular gyrus (MNI: x, y, z=-45, -36, 51) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51). Compared with HC group, the DC of two patient groups increased in the right inferior temporal gyrus (MNI: acute x, y, z=63, -27, -21; chronic x, y, z=63, -21, -27); the DC of acute bereaved PTSD group decreased in the right temporal pole (MNI: x, y, z=45, 21, -15) and the right orbital inferior frontal gyrus (MNI: x, y, z=48, 24, -12), while the DC of chronic bereaved PTSD group decreased in the left inferior parietal angular gyrus (MNI: x, y, z=-45, -36, 51) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51). Compared with chronic bereaved PTSD group, the DC of acute bereaved PTSD group increased in the left inferior parietal angular gyrus (MNI: x, y, z=-33, -39, 42) and left postcentral gyrus (MNI: x, y, z=-45, -33, 51), while decreased in the right temporal pole (MNI: x, y, z=51, 12, -9), right orbital inferior frontal gyrus (MNI: x, y, z=42, 21, -15) and bilateral medial superior frontal gyri (MNI: left x, y, z=0, 57, 15; right x, y, z=3, 57, 15). In chronic bereaved PTSD group, the DC of the left postcentral gyrus was negatively correlated with C1 (avoid trauma-related thoughts, feelings) score in CAPS ( r=-0.606, P=0.028). In acute bereaved PTSD group, the DC of the left medial superior frontal gyrus was negatively correlated with D4 (high vigilance) score ( r=-0.416, P=0.020). Conclusion:There exist functional abnormalities of multiple brain regions in acute and chronic bereaved parents with PTSD.The high arousal symptoms of the former may be related with the abnormalities of prefrontal-amygdala neural circuit, while the latter show higher avoidance which may be associated with the dysfunction of somatosensory brain regions such as postcentral gyrus.
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OBJECTIVE：To establish a method for the determination of pyrrotinib concentration in plasma ，and apply it in clinic. METHODS ：After precipitated with methanol ，the plasma sample was determined by LC-MS/MS using imatinib as internal standard. The determination was performed on Ultimate AQ-C 18 column with mobile phase consisted of methanol （containing 0.1％ formic acid ）and water （containing 0.1％ formic acid ）（gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was 40 ℃，and the sample size was 5 µL. The ion source was electrospray ionization source ，and the positive ion scanning was carried out in multiple reaction mode. The ion pairs for quantitative analysis were m/z 583.4→138.3（pyrrotinib）and m/z 494.5→ 393.4（internal standard ），respectively. Thirty breast cancer patients taking pyrrotinib were collected from the Affiliated Hospital of Qingdao University during Jun.-Nov. 2020 to determine their steady-state trough concentrations of pyrrotinib after a week of treatment. RESULTS ：The linear range of pyrrotinib were 5-300 ng/mL（r＝0.999 3）. The lower limit of quantification was 5 ng/mL. RSDs of intra-day and inter-day were not higher than 9.30％，and relative errors （REs）ranged －6.70％-5.04％. REs of stability tests were in the range of －1.92％-5.42％. The extraction method ，matrix effect and residual effect did not affect the quantitative analysis of the substance to be tested. The steady-state trough concentrations of pyrrotinib were 32.6-82.8 ng/mL，with an average plasma concentration of 53.8 ng/mL；there was about 2.54 fold individual difference. CONCLUSIONS ：Established LC-MS/MS method is simple ，sensitive and accurate ，and can be used for the plasma concentration monitoring of pyrrotinib in breast cancer patient.
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OBJECTIVE： To study the effects of Wuzhi soft capsule and imatinib mesylate tablet on the pharmacokinetics of imatinib in rats. METHODS： The rats were divided into single administration group and consecutive administration group. The single administration group was divided into imatinib group one （ig administration of blank soybean oil+imatinib suspension 10 mg/kg）， low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group （ig administration of Wuzhi soft capsule solution 134， 268， 536 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given imatinib suspension intragastrically 30 min after intragastric administration of blank soybean oil/Wuzhi soft capsule solution. The consecutive administration group was divided into imatinib group two （ig administration of blank soybean oil+imatinib suspension 10 mg/kg）， Wuzhi soft capsule low-dose+imatinib group （ig administration of Wuzhi soft capsule solution 134 mg/kg+imatinib suspension 10 mg/kg）， with 6 rats in each group. Each group was given blank soybean oil/Wuzhi soft capsule solution intragastrically for consecutive 14 d， once a day； 30 min after last administration， ig imatinib suspension. About 100 μL blood was collected before imatinib， 0.5， 1， 2， 2.5， 3， 4， 5， 6， 8， 12， 24 and 36 h after medication. The plasma concentration of imatinib was determined by HPLC-MS/MS. The pharmacokinetic parameters were fitted by using DAS 2.0 software. RESULTS： After single administration， compared with imatinib group one， cmax， t1/2， AUC0-36 h and AUMC0-36 h in low-dose， medium-dose and high-dose of Wuzhi soft capsule+imatinib group were increased significantly （P＜0.05 or P＜0.01）. After consecutive administration， compared with imatinib group two， cmax， t1/2 and AUMC0-36 h of imatinib+low-dose of Wuzhi soft capsule group were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： Single administration and consecutive administration of Wuzhi soft capsule influence the pharmacokinetics of imatinib， increase plasma concentration of imatinib and prolong half-time.
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Objective To investigate the value of the hippocampal subfield's MRI T2 signal intensity in evaluating the effect of the hydrochloric donepezil for mild cognitive impairment(MCI).Methods 20 MCI patients with hydrochloric donepezil (treatment group) and 20 patients with placebo (control group) were scanned by MRI using FSE-T2 sequence.The margin of hippocampal subfields was outlined manually for each side to measure the MRI T2 signal intensity.The relationship between hippocampal MRI T2 signal intensity and MMSE scores was analyzed in the treatment group.Results Before the treatment, there was no significant difference of the MRI T2 signal intensity between groups.After the treatment, the MRI T2 signal intensity in the bilateral head of the treatment group was significantly decreased compared with the control group(P<0.05).There was an inverse relationship between the MRI T2 signal intensity of the bilateral hippocampal head and MMSE scores in the treatment group(P<0.05).Conclusion The MRI T2 signal intensity in the bilateral hippocampal head could be regarded as a valuable marker in making clinical diagnosis and evaluating the effect of the treatment for MCI in its early stage.
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Objective:To explore the relationship between CD244 and the phenotype and function of CD56bright NK cells of patients with active pulmonary tuberculosis.Methods: PBMCs were isolated from peripheral blood by density gradient centrifugation.The expression of CD244,CD94,NKG2D on the CD56bright NK cells from the active pulmonary tuberculosis patients and healthy controls was detected by flow cytometry.And then analyzed the relationship of the expression of CD244 with Tim3,CD27,CD62L,CCR7,IFN-γ and CD107a in CD56bright NK cells by flow cytometry.Results: The expression of CD244 on the CD56bright NK cells showed no significant difference between the patients with active pulmonary tuberculosis and healthy controls without MTB antigen.The expression of CD244 was significantly increased on CD56bright NK cells of patients with tuberculosis stimulated with MTB antigen.The expression of CD94 and NKG2D on CD56bright NK cells showed no difference between patients and healthy controls.The proportion of Tim3+ cells in CD244+CD56bright NK cells was significantly higher than CD244-CD56bright NK cells.While the expression of CD62L and IFN-γ decreased significantly in CD244+CD56bright NK cells.The expression of CD107a on CD56bright NK cells was not significantly different between CD244+ cells and CD244-cells.Conclusion: The expression of CD244 on CD56bright NK cells in patients with active pulmonary tuberculosis increased significantly,maybe inhibit IFN-γ co-work with Tim3.CD244 has nothing to do with degranulation of CD56bright NK cells.
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@#Objective To apply the MRI T2 signal intensity of hippocampal subfield in patients with amnestic mild cognitive impairment (aMCI) as early imageology. Methods From October, 2014 to August, 2015, 20 aMCI patients accepted cognitive training (training group), 20 aMCI patients accepted speech communication (speech group), and 20 age-and gender-matched healthy old people (control group) were scanned with MRI using FSE-T2 sequence. The margin of hippocampal subfields were outlined manually for each side to measure the T2 sig-nal intensity. The correlation between hippocampal T2 signal intensity and the scores of Mini-Mental State Examinatlon (MMSE) was ana-lyzed in the training group. Results Before treatment, T2 signal intensity in the bilateral hippocampal head was significantly high in the aM-CI patients compared with that in the control group (P<0.05). After treatment, T2 signal intensity in left hippocampal head decreased in the training group compared with that in the speech group (P<0.05), similar to the control group (P>0.05). There was negative correlation be-tween left hippocampal head's T2 signal intensity and the scores of MMSE in the training group before and after treatment (r=-0.61, r=-0.54, P<0.05). Conclusion The T2 signal intensity in left hippocampal head may respond to the cognitive function in patients with aMCI in the early stage, that could be used for diagnosis and evaluation in clinic.
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OBJECTIVE:To investigate the effect of Wuzhi soft capsule on the pharmacokinetics of sirolimus in rats. METH-ODS:Wistar rats were randomly divided into 5 groups,with 6 rats in each group. They were given very low-dose,low-dose,me-dium-dose and high-dose of Wuzhi soft capsule(67,134,268 and 536 mg/kg)ig or blank solvent,respectively;and then given si-rolimus 0.4 mg/kg. The blood 100 μl was sampled by capillary eyes before giving sirolimus(0 h)and 0.5,0.75,1,1.5,2,2.5, 3,4,6,8,12,24 and 36 h after giving sirolimus and put into edetic acid anticoagulation tube. Blood concentration of sirolimus was assayed by LC-MS/MS. The pharmacokinetic parameter was calculated by DAS 2.0 software using non-compartment model. RESULTS:The pharmacokinetic parameters of sirolimus in very low-dose,low-dose,medium-dose and high-dose groups and blank solvent group were cmax of(6.79±1.15),(17.40±3.13),(21.24±3.14),(22.06±4.82),(2.80±0.72)ng/ml;t1/2 of(11.01± 0.82),(12.20±2.02),(12.28±2.38),(12.36±0.73),(10.59±0.69)h;AUC0-∞ of(85.79±15.26),(162.18±41.75),(273.12± 73.69),(268.79±28.46),(36.72±3.01)ng·h/ml,respectively. Compared with blank solvent group,cmax and AUC0-∞ of sirolimus were all increased in very low-dose,low-dose,medium-dose and high-dose groups,but t1/2 changed slightly. CONCLUSIONS:Wu-zhi soft capsule can substantially enhance the absorption of sirolimus in rats.
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Objective To estimate the diagnostic value of dual-energy CT in gouty arthritis.Methods English and Chinese litera-tures publicated before May 2014 were searched in PubMed,Embase,Cochrane and Wanfang database.Available literatures were selected according to the inclusion and exclusion criterias.Sensitivity,specificity with 95% confidence interval (95% CI)was pooled with bivariate random-effects model.Hierarchical weighted symmetric summary receiver-operating curve (HSROC)was also used in estimating.Meta-regression and sensitivity analysis were used to explore the potential sources of heterogeneity.Results Nine studies were included in the analysis.The pooled sensitivity,specificity and 95% CI were 92%(84-96%)and 88%(83-92%)respectively, area under the HSROC curve was 0.91 (0.88-0.93).There was substantial heterogeneity between studies(I 2 =85%).Conclusion Dual-energy CT is accuracy in diagnosing gouty arthritis.The sources of heterogeneity was not been explored.
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Objective:To compare the mRNA expression of IRG1in PBMCs from patients with TB, individual with latent infection and healthy controls, and investigate its diagnostic value for Mycobacterium tuberculosis infection.Methods: The mRNA expression of IRG1 from PBMCs stimulated with Mtb-specific antigens was quantitatively detected by quantitative real-time PCR ( qPCR).Receiver-operating-characteristic ( ROC) curves were used to determine the cutoff points yielding the highest specificity and sensitivity,and discriminative ability was evaluated by the area under the ROC curve.Results: The mRNA expression of IRG1 in healthy controls was significantly lower than that in patients with tuberculosis and LTBI ( P0.01536 ) to identify Mycobacterium tuberculosis infection was 0.91, with 76.47% sensitivity, 96.30% specificity, LR 20.65,and 85.2% of cases correctly classified.Conclusion: IRG1 may be used as a biomarker for diagnosing Mycobacterium tuberculosis infection.
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Objective To observe the effect and safety of intravesical perfusion of theprubicin ( THP) on postoperative recurrence of normuscle invasive bladder cancer .Methods According to digital table , a total of 58 cases received bladder cancer surgery were randomly divided into observation group and control group .All patients were treated by TURBt surgery .Patients in observation group were treated by THP intravesical perfusion , while patients in control group were treated by intravesical perfusion of mitomycin ( MMC) .A 1-year follow-up was conduc-ted to evaluate the recurrence rate and the toxicity .Results The recurrence rate of observation group in the follow-up period was 10.3%,while the control group was 20.7%,the difference was significant (χ2 =13.880,P0.05).The incidence rate of Ⅱ-Ⅲgrade toxicity in the observation group was 6.8%,while the control group was 17.2%,the difference was significant (χ2 =16.960,P <0.05). Conclusion The THP intravesical perfusion can prevent postoperative recurrence of normuscle invasive bladder cancer,with less toxicity.THP is effective,safe and reliable.
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Objective To evaluate the effect of the percutaneous nephrolithotomy ( PCNL) in the manage-ment of complicated upper ureteric calculi , compared with retroperitoneal laparoscopic ureterolithotomy ( RLU ) . Methods Seventy-one cases with complicated upper ureteric calculi were retrospectively investigated ( PCNL group 23 cases,RLU group 29 cases).Clinical data including operation time ,stone free rate and the surgical complications were statistically analyzed .Results All the operations were successful in all 52 cases.Compared with the RLU group,the PCNL group had a significant shorter operation time [(45.12 ±11.56)min vs (82.03 ±12.45)min,t=10.13,P<0.01],and significant difference were detected .A week after the operation,the PCNL group showed a stone free rate of 95.6%(22/23) while the RLU group 100.0%(29/29),and no significant difference were detec-ted.No significant complications ,such as intraoperative or postoperative bleeding and damage to surrounding organs , were detected.The patients were followed up for 6 to 12 months(mean,9 months),and no recurrent stones or ureteral stricture were developed during the period .Conclusion Both PCNL and RLU are safe and effective for complicated upper ureteral calculi.The appropriate method depends on the patients′specific conditions,the unit equipments and the experience of operator .
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Objective To discover T cell reactive peptides of mycobacterium tuberculosis antigen Rv2608 for treatment or adjuvant treatment for tuberculosis.Methods The T cell epitopes of Rv2608 were predicted by bioinformatics.The long-chain peptides were screened with strong affinity with HLA-A0201,HLA-A1101,and HLA-A2402.The physical and chemical characters of the peptides were predicted.The stable and hydrophilic peptides for chemical synthesis were selected.The T cell reactivity of the peptides in patients with active tuberculosis was detected by ELISPOT.The results were compared with the clinical diagnosis kits TSPOT.TB.Results Four peptides of Rv2608 were predicted and screened,and they could be active T cells of patients with active TB.Rv2608p3 was the most efficient to prime the T cell response.Conclusions Software prediction was consistent with the result of ELISPOT.Rv2608p3 might be the candidate for therapeutic vaccine for tuberculosis.
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Objective To explore the points of nursing cooperation during double pedicle of forehead flap for repair of mouth scar contracture deformity.Methods The psychological nursing,equipment and instrument preparation,cooperation of instrument nurses and circuit nurses were summarized in 15 cases of an expanded forehead flap for repair of mouth scar contracture.Results The operation process was smooth,all the flaps survived,repair effect was good,no complications occurred.Conclusions Burn plastic surgery specialist nurses in operation room giving careful preoperative visit and nursing risk assessment can alleviate the psychological pressure of the patients,reduce the defects of nursing.Close cooperation during operation and effective environmental management is critical for successful completion of operation.
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Objective To investigate the feature of Th1 cytokines induced by Mtb-specific antigen in patients with refractory pulmonary tuberculosis.Methods 28 patients with refractory pulmonary tuberculosis,67 patients with first-treated pulmonary tuberculosis,and 25 healthy controls with positive T.spot (LTBI group) were enrolled.IFN-γ,IL-2 and TNF-α in supernatants from PBMCs stimulated with ESAT-6 and CFP-10 were analyzed with Bender Flowcytomix on flow cytometry.Results The levels of the three cytokines were utmost high in patients with first-treated pulmonary tuberculosis.The lowest level of IFN-γ and IL-2 were induced in patients with refractory pulmonary tuberculosis,and were significantly lower than the LTBI group(Mann-Whitney U ＝ 105.5,162.5,P ＜ 0.01).Conclusions The immunotherapy with IFN-γ and IL-2 may play a role in treatment for refractory pulmonary tuberculosis but not for most of first-treated pulmonary tuberculosis.
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Objective To study the feature of MCP-1 in plasma of active pulmonary tuberculosis patients and the correlation of MCP-1 obtained from PBMCs stimulated with specific Mtb peptides with IFNγ.Methods 20 patients with active pulmonary tuberculosis and 16 healthy controls with positive PPD were enrolled.The concentration of MCP-1 and IFN-γwas analyzed with Bender Flowcytomix on flow cytometry.Results No statistical difference of MCP-1 concentration in plasma was found between TB patients and controls [(263.8 ± 25.31)pg/ml and(212.1 ± 18.04)pg/ml,P ＞ 0.05].But TB patients with continuous respiratory symptoms showed higher MCP-1 in plasma.The concentration of MCP-1 and IFN-γwas significantly elevated in PBMCs culture supernatants.It was significantly higher in TB patients than in controls [(21460 ±3376)pg/ml vs(10910 ±2141)pg/ml,P ＜0.01].There was no correlation between the concentration of MCP-1 and IFN-γ.Conclusions The concentration of MCP-1 in plasma may be related to the progress of the pulmonary tuberculosis.MCP-1 stimulated by Mtb-specific peptides may be one of the biomarkers for TB diagnosis.
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Objective To study the feature of MIG and IFN-γ obtained from PBMCs stimulated with Mtb specific antigens and the potential value in the differential diagnosis of active pulmonary tuberculosis from bacterial pneumonia and primary lung cancer. Methods 90 patients with active pulmonary tuberculosis and 31 patients with bacterial pneumonia and primary lung cancer were enrolled. MIG and IFN-γin supernatants from PBMCs stimulated with Mycobacterium tuberculosis-specific antigens were analyzed with Bender Flowcytomix on flow cytometry. The diagnostic values were established based on receiver operating characteristic curve analysis. Results PBMCs stimulated with Mtb-specific antigens produced significantly higher levels of MIG compared with IFN-γ The level of MIG in active pulmonary TB patients was significantly higher than in controls(3023.0 pg/ml vs 112.5 pg/ml, P ＜0.0001). The MIG and IFN-γtests were positive in 96. 8 and 86. 7% of the TB patients, the specificity was up to 94. 4 and 87. 1%. With combination of MIG and IFN-γtests, the positive rate increased among TB patients to 97. 8% without a significant decrease in specificity. Conclusions The responses of the MIG and IFN-γagainst to Mtb-specific antigens could be used to discriminate newly-treated active pulmonary tuberculosis fiom bacterial pneumonia and primary lung cancer. Combination of MIG and IFN-γ might be a simple and quick approach to diagnosis newly-treated active pulmonary tuberculosis.
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Objective To study the expression of CD27 and CD28 in antigen-specific CD4~+T cells in patients with pulmonary tuberculosis and healthy people, and understand the role of differentiated stages of CD4~+T cells in the pathogenesis of tuberculosis. Methods The expression of CD27 and CD28 was analyzed by CD4, CD154, CD27 and CD28 staining and flow cytometry. The distributions of CD27 and CD28 in antigen-specific CD4~+T cells were compared between patients with pulmonary tuberculosis and healthy controls. Results In patients of pulmonary tuberculosis, the frequencies of CD27 + CD28 + (early differentiated stage), CD27~- CD28~+ and CD27~+ CD28~- (intermediate differentiated stage), CD27~- CD28~-(fully differentiated stage) T cell subsets in antigen specific CD4~+T cells were (49. 55 ±6. 15)%, (26. 85 ±3. 87)% ,(7. 2 ± 1.37)% and ( 16. 35 ±3.97)%, respectively. In healthy controls, the frequencies of the four subsets in antigen-specific CD4~+T cells were ( 51.81 ± 4. 94 ) %, ( 29. 83 ± 5.33 ) %, ( 12. 65 ±4. 48)% and (5.7±2)%, respectively. The early differentiated CD4~+T cell was the major subset both in patients and healthy people, however, which had significant difference compared with the fully differentiated subset ( t = 2. 26, P < 0. 05 ). Conclusion The population frequency of the fully differentiated CD4~+T cells in patients with pulmonary tuberculosis was significantly higher than that in healthy people. This suggested that the differentiation degree of the antigen-specific CD4~+T cell might be related with pulmonary tuberculosis.
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Objective To study population frequencies of CD4+,CD154+ T cell subset in patients with pulmonary tuberculosis and controls with positive PPD reaction. Methods Flow cytometry was used to detect the CD4+,CD154+ T cell subset, the population frequen-cies in patients with pulmonary tuberculosis and controls were compared. Results The expression level of CD154 was higher when PE-la-beled CD154 antibody was added during stimulation period, compared with CD154 labeling after stimulation(1.51±0. 36/0. 40±0. 13, P <0.05). The CD154+ cells were not detectable in fresh isolated CD4+ T cells, but significantly increased after stimulation with specific anti-gens. The population of CD4+, CD154+ T cell subset was significantly reduced in patients with active pulmonary tuberculosis, compared with healthy controls with PPD positive reaction(0. 72±0. 32/1.65±0. 76, P <0. 01). Conclusions The population of CD4± ,CD154± T cell subset was significantly reduced in patients with active pulmonary tuberculosis, which indicated that it may play an important role in the de-velopment of tuberculosis.