The value of peripheral blood sIL-2R,CD4+/CD8+and TNF-α in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis / 国际检验医学杂志

Objective To investigate the value of peripheral blood soluble interleukin-2 receptor(sIL-2R),CD4+lymphocyte percentage/CD8+lymphocyte percentage ratio(hereinafter referred to as CD4+/CD8+)and tumor necrosis factor-α(TNF-α)in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis.Methods A total of 102 elderly patients with newly treated active tu-berculosis admitted to the hospital from December 2019 to December 2022 were enrolled in the study as the observation group,and 102 healthy people aged 60 and older who underwent physical examination in the hos-pital during the same period were enrolled as the control group.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood were compared between the two groups,and the correlations between sIL-2R,TNF-α and CD4+/CD8+were analyzed.The observation group was treated with 2HRZE/4HR anti-tuberculosis treatment regimen.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood of patients with different efficacy before treatment,1 month and 6 months after treatment in the observation group were compared.The correla-tion between sIL-2R,CD4+/CD8+,TNF-α levels and therapeutic effect was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of indicators in evaluating the efficacy of chemo-therapy in elderly patients.Results The levels of sIL-2R and TNF-α in the observation group were higher than those in the control group,while CD4+/CD8+was lower than that in the control group,and the differ-ences were statistically significant(P＜0.05).In the observation group,sIL-2R and TNF-α were negatively correlated with CD4+/CD8+(P＜0.05),sIL-2R was positively correlated with TNF-α(P＜0.05).After 1 month and 6 months of treatment,the levels of sIL-2R and TNF-α in patients with apparent efficacy were low-er than those in patients with efficacy,and the latter were lower than those in patients with no effect,while the CD4+/CD8+in patients with apparent efficacy was higher than that in patients with efficacy,and the latter was higher than that in patients with no efficacy,and the differences were statistically significant(P＜0.05).The levels of sIL-2R and TNF-α were negatively correlated with the efficacy(P＜0.05),and CD4+/CD8+was positively correlated with the efficacy(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of sIL-2R,CD4+/CD8+,and TNF-α used in combination to assess efficacy was significantly greater than the AUCs of the single indicators used in the assessment at each time point of treatment(P＜0.05),and the AUC of the combination of the indicators was greater after 6 months of treatment than after 1 month of treatment(P＜0.05).Conclusion The levels of sIL-2R,CD4+/CD8+and TNF-α are closely related to the ef-ficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis,and the combina-tion of the above indicators has certain reference value in evaluating the efficacy of chemotherapy in patients.

Differences of gene expression profiles of different subpopulations of exhausted T cells in patients with active pulmonary tuberculosis / 中华传染病杂志

Objective:To explore the differences of gene expression profiles of precursors of exhausted T cells (Tpex) and terminal exhausted T cells (Tex) in the peripheral blood of patients with active pulmonary tuberculosis (ATB).Methods:Twenty-five cases of ATB, 13 cases of latent tuberculosis infection (LTBI) and 10 health controls were enrolled from January 2021 to October 2022 in the Fifth People′s Hospital of Wuxi. The proportions of Tpex and Tex in the peripheral blood mononuclear cells (PBMCs) of the three groups were detected by flowcytometry. PBMCs of ATB were separated into Tpex and Tex by fluorescence-activated cell sorting. RNA-sequencing was performed and up-regulated and down-regulated genes were screended. Differently expressed genes were analyzed by gene set enrichment analysis of gene ontology (GO) to find regulatory pathways affecting cell metabolism and function. Wilcoxon matched-pairs signed rank test, Kruskal-Wallis test and Dunn multiple comparsion test were used for statistical analysis.Results:The proportion of Tpex in ATB group was 2.86%(1.74%), which was lower than 7.93%(6.16%) of Tex, and the difference was statistically significant ( Z=-3.91, P<0.001). The proportions of Tpex and Tex in LTBI group were 9.47%(6.26%) and 7.43%(5.48%), respectively, and the difference was not statistically significant ( Z=-0.93, P=0.345). The proportions of Tpex and Tex in healthy control group were 8.42%(2.69%) and 6.49%(5.14%), respectively, with no statistical significance ( Z=-1.36, P=0.170). There was statistical difference of the proportion of Tpex among the three groups ( H=21.93, P<0.001), and the proportion of Tpex in ATB group was lower than those in LTBI and heathy control groups, and the differences were both statistically significant ( Z=4.16, P<0.001 and Z=3.34, P=0.003, respectively), while the proportions of Tex in these three groups were not statistically different ( H=2.17, P=0.338). Compared with Tex, the gene expressions of memory markers, such as B-cell lymphoma 2 of Tpex were up-regulated, and the gene expressions of exhausted markers, such as lymphocyte activation gene 3 were down-regulated. In terms of cellular metabolism, the gene expressions of mitochondrial protein complex, mitochondrial matrix and oxidative phosphorylation of Tpex were up-regulated, and the gene expressions of glycolysis were down-regulated. The gene expressions of pyruvate metabolism in Tex were up-regulated, and the gene expressions of CD4 + T lymphocyte activation and differentiation and glycolytic process in Tpex were down-regulated. Conclusions:Tpex in ATB express more characteristics of memory cells and less features of exhausted markers compared with Tex, and the function of mitochondria of Tpex preserves well.

Correlation of macrophage-related cytokines and silent information regulator 1 and forkhead box protein O3 levels in peripheral blood mononuclear cells in patients with active pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To explore the correlation between the levels of silent information regulator 1 (SIRT1) and forkhead box protein O3 (FOXO3) in peripheral blood mononuclear cells of patients with active pulmonary tuberculosis (APTB) and macrophage-related cytokines-inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1). Methods　A total of 64 APTB patients who were treated in Yubei Hospital, the First Affiliated Hospital of Chongqing Medical University from January 2020 to December 2021 were gathered as the APTB group, 59 people with latent tuberculosis infection (LTBI) were gathered as the LTBI group, and 62 healthy people were gathered as the control group. Quantitative real-time PCR (qPCR) method was performed to measure the levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells. The enzyme-linked immunosorbent assay (ELISA) was performed to measure serum iNOS and Arg-1 levels; ROC curve was used to analyze the value of SIRT1 mRNA and FOXO3 mRNA levels in the differential diagnosis of LTBI and APTB; Pearson correlation was performed to analyze the correlation of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients with serum iNOS and Arg-1 levels. Results　The levels of SIRT1 mRNA, FOXO3 mRNA and serum iNOS in peripheral blood mononuclear cells decreased in control group, LTBI group and APTB group, and the level of serum Arg-1 increased in turn (P<0.05). The AUCs of SIRT1 mRNA and FOXO3 mRNA in differential diagnosis of LTBI and APTB were 0.876 and 0.887, respectively, the sensitivity was 71.2% and 76.3%, and the specificity was 96.9% and 90.6% respectively. The levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients were positively correlated (r=0.500, P<0.05), and they were positively correlated with serum iNOS and negatively correlated with serum Arg-1 (P<0.05). The SIRT1 mRNA, FOXO3 mRNA and serum iNOS in peripheral blood mononuclear cells of APTB patients after 6 months of treatment were higher than those before treatment, and serum Arg-1 was lower than before treatment (P<0.05). Conclusions　The levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients are low, and they are positively correlated with macrophage-related cytokine iNOS and negatively correlated with Arg-1.

Application value of chest CT angiography in active pulmonary tuberculosis complicated with pulmonary embolism / 国际生物医学工程杂志

Objective:To investigate the imaging characteristics of chest CT angiography in patients with active pulmonary tuberculosis complicated with pulmonary embolism, so as to improve the detection rate of active pulmonary tuberculosis complicated with pulmonary embolism.Methods:The clinical data of 103 patients with active pulmonary tuberculosis treated in Tianjin Haihe Hospital from January 2013 to January 2020 were retrospectively analyzed, including general conditions, symptoms and complications. According to the occurrence of pulmonary embolism, the patients were divided into active pulmonary tuberculosis complicated with pulmonary embolism group (study group, n=43) and active pulmonary tuberculosis without pulmonary embolism group (control group, n=60). The time between the onset of pulmonary embolism and the onset of tuberculosis of the patients in the study group was collected. The chest CT imaging characteristics of the patients of two groups were analyzed. The imaging characteristics, embolism distribution and secondary changes of the patients in the study group were summarized. Results:Time from onset of tuberculosis to pulmonary embolism of the patients in the study group was about 60 days (14 days to 75 days). The incidence of chest tightness and dyspnea of the patients in the study group was significantly higher than that in the control group (all P<0.05). The number of lung lobes involved in lung lesions of the patients in the study group was significantly higher than that in the control group ( P<0.05). The incidence of lesions in the middle lobe of the right lung, the tongue lobe of the left lung and the lower lobes of both lungs of the patients in the study group was higher than that in the control group (all P<0.05). The incidence of peripheral pulmonary embolism was significantly higher than that of central pulmonary embolism ( P<0.05). However, the incidence of atelectasis, pulmonary artery widening, and right heart enlargement in the patients with central pulmonary embolism was significantly higher than that in the patients with central pulmonary embolism (all P<0.05). Conclusions:Multi-slice spiral CT chest angiography can show some important imaging manifestations of patients with active pulmonary tuberculosis and pulmonary embolism, which is helpful for the early detection of the disease and the improvement of its prognosis. Multi slice spiral CT chest angiography can show some important imaging manifestations of patients with active pulmonary tuberculosis complicated with pulmonary embolism, and timely detection is helpful to improve the prognosis of patients with active pulmonary tuberculosis complicated with pulmonary embolism.

Pre-existing chronic medical illnesses and follow up status among active pulmonary tuberculosis cases in a district population

@#Introduction: The knowledge of pre-existing medical illnesses and their follow up status among active pulmonary tuberculosis (PTB) subjects can help in tuberculosis (TB) control programme. The aims of our study were to examine: the prevalence of pre-existing chronic medical illnesses, the follow up status of known pre-existing co-morbid and to distinguish between diagnosed and undiagnosed preexisting tuberculosis related chronic medical illnesses among our active PTB subjects. Methods: We conducted a retrospective review of demographic and clinical data of active PTB subjects that were diagnosed between January 2015 and June 2017 in the district of Manjung, Perak, Malaysia. Among the 302 TB clinical notes reviewed, 253 patients were included. Subjects below the age of 18 years and whose follow up centres for their medical illnesses that were located outside of Manjung were excluded. Demographic and clinical data were collected using pre-tested data collection form by trained investigators. The data was analysed using SPSS Version 20.0. Results: We identified diabetes mellitus as the most prevalent pre-existing co-morbid (77 cases) and almost 90% (68 cases) of these diabetic subjects were diagnosed prior to active PTB diagnosis. This was followed by Human Immunodeficiency Virus and Hepatitis C infection which accounted for 12.0% (30 cases) of the study populations. Among 132 subjects who had pre-existing chronic medical illnesses, only 74 subjects (29%) were under regular follow up at healthcare facilities in Manjung prior to PTB diagnosis. Conclusion: Overall, our research provides evidence on the existence of wide variation of clinical background among active PTB subjects.

Diagnostic value of lymphocyte subset classification for active pulmonary tuberculosis in renal transplant recipients / 器官移植

Objective To evaluate the clinical value of lymphocyte subset classification in the diagnosis of active pulmonary tuberculosis in renal transplant recipients. Methods Clinical data of 52 recipients undergoing renal transplantation were retrospectively analyzed. According to the results of imaging and etiological examination, 52 recipients were divided into the stable group(n=19), tuberculosis group (n=9), bacteria group (n=12) and fungi group (n=12), respectively. The renal function of recipients was compared, and the proportion and absolute value of lymphocyte subset were analyzed and compared among four groups. The diagnostic value of lymphocyte subset classification for active pulmonary tuberculosis after renal transplantation was evaluated. Results Compared with the stable group, the levels of blood urea nitrogen and serum creatinine in the tuberculosis group, bacteria group and fungi group were significantly increased (all P < 0.05). The proportion of CD3+, CD8+, CD4+, natural killer (NK) cells and CD19+ lymphocyte subsets were not significantly different (all P>0.05). And the absolute values of CD3+, CD8+, CD4+, NK cells and CD19+ lymphocyte subsets were significantly decreased (all P < 0.05). The proportion of CD8+ lymphocyte subset in the tuberculosis group and fungi group was significantly higher than that in the bacteria group (both P < 0.05). The optimal cut-off value of CD8+ lymphocyte subset ratio in the differential diagnosis of active pulmonary tuberculosis and bacterial pneumonia was 33.27%, and the sensitivity and specificity were 0.889 and 0.833, respectively. The area under the curve (AUC) was 0.880. Conclusions The classification of lymphocyte subset can provide auxiliary diagnostic basis for differential diagnosis and individualized treatment of active pulmonary tuberculosis and bacterial pneumonia in renal transplant recipients.

Whole Blood Interferon-gamma Release Assay Is Insufficient for the Diagnosis of Sputum Smear Negative Pulmonary Tuberculosis

PURPOSE: We investigated the value of an interferon-gamma release assay (IGRA) for the diagnosis of active pulmonary tuberculosis (PTB) among sputum smear negative PTB suspects in an environment with intermediate burden of PTB and high Bacillus Calmette-Guerin (BCG) vaccination rate. MATERIALS AND METHODS: We retrospectively reviewed IGRA, medical records, chest PA and CT scan of PTB suspects seen at Gangnam Severance Hospital, Seoul, Korea from Oct. 2007 to Apr. 2013. "Active PTB" was diagnosed when 1) M. tuberculosis culture positive, 2) confirmation by pathologic examination; or 3) clinical findings compatible with TB. RESULTS: Of 224 sputum smear negative PTB suspects, 94 were confirmed as having active PTB. There were no statistically significant differences in the diagnostic yield of IGRA between immunocompromised and immunocompetent sputum smear negative PTB suspects. IGRA did show superior sensitivity [81.9%, 95% confidence interval (CI); 74.13-89.70%] in the diagnosis of sputum smear negative PTB when compared with chest high-resolution computed tomography (HRCT), tuberculin skin test (TST), and chest X-ray (p<0.001). Also, IGRA showed highest negative predictive value (82.7%, 95% CI; 75.16-90.15%) when compared with HRCT, TST and chest X-ray (p=0.023). However, combining the results of IGRA with those of HRCT, TST, or both did not increase any diagnostic parameters. CONCLUSION: Failure to increase diagnostic yields by combination with other diagnostic modalities suggests that additional enforcement with IGRA may be insufficient to exclude other diagnoses in sputum smear negative PTB suspects and to screen active PTB in an environment with intermediate TB prevalence and a high BCG vaccination rate.

Preliminary Study for Elevated Serum CXCL10 and CXCL11 in Active Pulmonary Tuberculosis Compared with the Other Pulmonary Diseases / 결핵및호흡기질환

BACKGROUND: CXCL10 and CXCL11, which are family of CXCR3 ligands, are expressed by lymphocytes and even by bronchial epithelial cells if the cellular immunity is activated. This study evaluated the potential utility of CXCL10 and CXCL11 in the serum for active pulmonary tuberculosis in comparison with lung cancer, which activates the cellular immunity, and benign lung diseases. METHODS: Patients who newly visited Pusan National University Hospital from January 2007 to December 2007 and were suspected of having lung cancer or tuberculosis were enrolled prospectively. The patients were classified pathologically and clinically into three groups, 47 with lung cancer, 18 with active pulmonary tuberculosis and 38 control patients with benign pulmonary disease. ELISA was used to determine the levels of CXCL10 and CXCL11 were determined in the serum. RESULTS: The level of CXCL10 and CXCL11 were significantly higher in the active pulmonary tuberculosis group than in the lung cancer and benign lung disease groups (p<0.001, Kruskal-Wallis). The level of CXCL11 was significantly higher in the lung cancer group than in the benign pulmonary disease group, but there was no significant difference in level of CXCL10 between the three groups (p<0.001, p=0.655, respectively, Mann-Whitney U). The level of CXCL10 in patients with stage III+IV lung cancer was significantly higher than those with stage I+II, but there was no significant difference in the level of CXCL11 between the groups (p<0.001, p=0.07, respectively, Mann-Whitney U). There was no significant difference in the level of CXCL10 and CXCL11 between those with the presence and absence of lung cancer metastasis. There was a significant correlation between the level of CXCL10 and CXCL11 (r=0.223, p<0.001). CONCLUSION: CXCL10 and CXCL11 may be a potential useful markers for active pulmonary tuberculosis if used alongside other diagnostic methods.

Development of a diagnosis model for active pulmonary tuberculosis using mass spectrometry and pro-tein chip / 中华微生物学和免疫学杂志

Objective To develop a diagnosis model for active pulmonary tuberculosis. Methods The proteomic fingerprinting of 264 sera from active tuberculosis patients and controls were analyzed using the surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) and protein-chip technology. The peaks were detected and filtrated by Ciphergen PrnteinChip(R) Software (version 3.1.1). Using the Biomarker Pattern 5.0 software, a diagnostic model was developed for diagnosis of active tuberculosis. Re-sults Fifty protein peaks were significantly different between the patients with active pulmonary tuberculosis and the controls with overlapping clinical features (P<0.01). Five protein peaks at 4360, 3311, 8160, 5723, 15173 m/z were chosen for the system classifier and the development of diagnosis model 1. The model differenti-ated the patients with active pulmonary tuberculosis from the controls with a sensitivity of 83.0%, and a speci-ficity of 89.6%. The diagnostic accuracy was up to 86.4%. Three protein peaks at 5643, 4486, 4360 m/z were chosen for the system classifier and the development of diagnosis model 2. The model differentiated the pa-tients with active pulmonary tuberculosis from the controls with a sensitivity of 96.9%, and a specificity of 97.8%. The diagnostic accuracy was up to 97.3%. Conclusion It might be a new diagnostic test for the de-tection of sera from the patients with active pulmonary tuberculosis using SELDI-TOF-MS and protein chip.

Analyses for the ?/? T Cell Receptor Gene Rearrangement and CDR3 Repertoire in Active Pulmonary Tuberculosis Patients / 中国免疫学杂志

Objective:To establish a method of multi-PCR to amplify the complete DNA sequence (CDS) of TCR ? and ? chain of the antigen-specific T lymphocytes in local pathologic specimen of active pulmonary tuberculosis patients, and to analyze ?/? T cell receptor gene rearrangement and CDR3 repertoire.Methods:The lymphocytes in bronchoalveolar lavage (BAL) of active pulmonary tuberculosis patients were separated. Following total RNA extraction, cDNA synthesis, Multi-PCR, recombinant clones construction, and sequencing, the CDS of TCR ? and ? chains from these lymphocytes were analyzed by using software of DNAstar and internet TCR resources.Results:24 of ? chain CDS and 13 of ? chain CDS from 3 samples of BAL were obtained. As for TCR ? chain, AV1S2 (54%), AV12S3 (41%), and AV12S2(5%) appeared frequently. BV2(38%), BV29S1(46%), BV14(3%), and BV4S2(3%) in TCR ? chain appeared more often. There were CDR3 diversities between samples and even in the same sample by amino acid sequence analysis, but there were a few identical or similar amino acid sequences. There was the same amino acid sequence of SVGTGTLHQETQY in CDR3 region of ? chain of BAL sample No.1 and No.2; The sequence of AVRDWAGNMLT appeared in two ? chains of BAL sample No.2 and No.3; Moreover, the sequence of AV…DNN…RLM appeared in ? chains of BAL sample No.2 and No.3.Conclusion:A method of Multi-PCR is used to amplify TCR ? and ? chain CDS of tuberculosis patients. There are characteristic T cell clones to proliferate,with TCR ? and ? chain repertiore skewing in local infective focus. The sequences of CDR3 in different TCR clones are mostly different but there are a few identical or similar sequences in the same patient or even between different patients. The identical amino acid sequences of CDR3 are possibly specific for recognizing MTB polypeptide.

Diagnostic Significance of the Serologic Test Using Antigen of Mycobacterium Tuberculosis for Antibody Detection by ELISA / 결핵

BACKGROUND: Diagnosis by direct microscopy and/or by culture of the Mycobacterium tuberculosis from body fluids or biopsy specimens is "Gold standard". However, the sensitivity of direct microscopy after Ziehl-Neelsen staining is relatively low and culture of mycobacteria is time consuming. Detection of mycobacterial DNA in clinical samples by the polymerase chain reaction is highly sensitive but laborious and expensive. Therefore, rapid, sensitive and readily applicable new tests need to be developed. So we had evaluated the clinical significance of serologic detection of antibody to 38 kDa antigen, which is known as the most specific to the M. tuberculosis complex, and culture filtrate antigen by ELISA in sputum AFB smear negative patients. METHOD: In this study, culture tests for acid fast bacilli with sputa or bronchial washing fluids of 183 consecutive patients who were negative of sputum AFB smear were performed. Simultaneously serum antibodies to 38 kDa antigen and unheated culture filtrate of M. tuberculosis were detected by an ELISA method. RESULTS: The optical densities of ELISA test with 38 kDa and culture filtrate antigen were significantly higher in active pulmonary tuberculosis cases than in non tuberculous pulmonary diseases (pO.05). In the smear-negative active pulmonary tuberculosis patients, the sensitivity of the ELISA using 38 kDa antigen and culture filtrate was 20.0% and 31.4%, respectively. The specificity was 95.3% and 93.9%, respectively. CONCLUSION: In active pulmonary tuberculosis but smear negative, the serologic detection of antibody to 38 kDa antigen and culture filtrate by ELISA cannot substitute traditional diagnostic tests and does not have clinically significant role to differenciate the patient with active pulmonary tuberculosis from other with non-tuberculous pulmonary diseases.

A Case of True Precocious Puberty Associated with Pituitary Microadenoma Treated with LHRH Agonist / 대한내분비학회지

Although tubercrlosis is one of the recognized causes of adrenal insufficiency, little is known about adrenal function in patients with active pulmonary tuberculosis. Patients with active pulmonary tuberculosis are at risk from sudden and unexpected death which can occur during the first few weeks of treatment. There are many reports that patients who received rifampicin as a part of their treatment appeared to show impairment in adrenocortical function when compared to a group who received anti-tuberculosis chemotherapy which did not include rifampicin. Adrenocortical function was studied in 15 patients(7 males, 8 females) with active pulmonary tuberculosis, before and 2-weeks after the anti-tuberculosis chemotherapy including rifampicin. At 08: 00 hour a base-line sample of venous blood was taken. One hour after the administration of 0.25mg of Synacthen, a further blood specimen was taken. The base-line and 1-hour specimens were analysed for plasma cortisol and electrolytes.All were initially found to have a normal cortisol response to rapid ACTH stimulation test. Following a 2-week course of anti-tuberculosis chemotherapy including rifampicin there was 1 case(6.6%) of a suboptimal response.Rifampicin, a powerful anti-tuberculosis drug, is a known inducer of the hepatic microsomal enzyme system and has been shown to cause an enhanced clearance of endogenous cortisol. Findings reported in this paper suggest that the adrenocortical function is compromised in some case(6.6%) of tuberculosis patients. It will therefore be necessary to undertake detailed investigations on the effect of treatment with daily and fully intermittent regimens containing rifampicin on the function of this endocrine gland.