[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

[Comparison of QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In Tube in the diagnosis of pulmonary tuberculosis].

Objective: To compare the screening value of QuantiFERON-TB Gold Plus (QFT-Plus) and QuantiFERON®-TB Gold in tube (QFT-GIT) in the auxiliary diagnosis of pulmonary tuberculosis (TB). Methods: A screening test was performed. Patients who were hospitalized in Guangzhou Chest Hospital and underwent QFT-GIT testing from October to December 2020 were prospectively included as research subjects, QFT-Plus testing was added. And the basic information, clinical manifestations, laboratory test results, imaging examinations and other data of these patients were collected. A total of 207 patients were included and divided into tuberculosis group and non-tuberculosis group according to these data. There were 124 cases in the tuberculosis group (94 confirmed patients and 30 clinically diagnosed patients), including 90 males and 34 females, aged 18-93 years, with a median age of 57 (38, 67) years. The non-tuberculosis group included 83 patients (16 patients with non-tuberculous Mycobacteria and 67 patients with other lung diseases), including 49 males and 34 females, with a median age of 60 (51, 68) years. The confirmed patients were subdivided into three grades of low, medium and high Mycobacteriam tuberculosis (MTB) bacterial load, and three grades of mild, moderate and severe pulmonary tuberculosis. The results of QFT-Plus and QFT-GIT were compared, and the levels of IFN-γ in different antigen tubes were compared. Differences between different groups were compared using Mann-Whitney U test and Kruskal-Wallis H test. Results: The QFT-Plus showed a high degree of agreement with the QFT-GIT (κ=0.786, 95%CI: 0.740-0.832), while the main discordant result was QFT-GIT negative/QFT-Plus positive, accounting for 15/17. The sensitivity of QFT-GIT was 80.7%(95%CI: 0.706-0.880), the specificity was 76.3%(95%CI: 0.649-0.850), the positive predictive value was 79.8%(95%CI: 0.697-0.873), and the negative predictive value was 77.3%(95%CI: 0.659-0.859), repectively. QFT-Plus showed a sensitivity of 84.3%(95%CI: 0.743-0.910), a specificity of 78.8% (95%CI: 0.679-0.868), and a positive predictive value of 80.5%(95%CI: 0.703-0.879), the negative predictive value being 82.9%(95%CI: 0.721-0.902), slightly improved to that of the QFT-GIT. Also, this study found that there were significant differences in IFN-γ values between different MTB load or disease severity (P<0.05). Conclusions: There is a good consistency between the QFT-Plus test and the QFT-GIT test, both of which show good application value in the auxiliary diagnosis of pulmonary tuberculosis. Moreover, because of the addition of tuberculosis-specific CD8 cell antigen, the QFT-Plus test has higher sensitivity, lower uncertainty and more application value. This study also found that the bacterial load and disease severity of patients with pulmonary tuberculosis may have a certain correlation with the measured value of IFN-γ.

[Signaling pathway of M2-type polarization induced by Mycobacterium tuberculosis-specific peptide E7 in monocyte-macrophages].

Objective: To explore the signal pathway of M2-type polarization induced by Mycobacterium tuberculosis (MTB)-specific peptide E7. Methods: Monocyte-macrophages were divided into blank control group, M1 positive stimulus group [co-stimulated with lipopolysaccharide and gamma interferon (IFN-γ)], M2 positive group(co-stimulated with IL-4 and IL-13), and E7 experimental group (with MTB-specificity polypeptide E7 stimulated). The expression of M1 type markers CD(16), IL-6, TNF-α and M2 type markers CD(163), CD(206), IL-10 were detected at 12, 18, 24 and 36 h. Furthermore, peroxisome proliferators-activated receptors-γ (PPAR-γ) blocker was used in the blank control group, M2-positive stimulus group and E7 experimental stimulus group. T test was used to compare the expression of PPAR-γ and CD(163) before and after the addition of blockers. Results: Compared with the positive control group and the blank control group, the expression of TNF-α in the E7 experimental group gradually reached the peak when macrophages were stimulated for 18 h(the relative expression was 20.02), and then the expression of TNF-α gradually decreased and the expression of CD(163) increased. The expression of CD(163) peaked at 24 h (the relative expression was 2.44). After adding the inhibitor, the expression of PPAR-γ in E7 stimulation group was lower than before blocking (before blocking 0.94±0.06, after blocking 0.69±0.09, P=0.028). CD(163) expression level was significantly lower than that before blocking (before blocking 3.95±0.61, after blocking 2.87±0.20, P=0.047). Conclusion: The MTB-specific peptide E7 induced differentiation of macrophages into M2 type, a process that may be involving PPAR-γ in just another kinase-signal transducer and activator of transcription pathway.

[Effects of c-erbB(2) on the hCG-induced progesterone production of rat luteal cells].

The effects of c-erbB(2) antisense oligodeoxynucleotides (antisense c-erbB(2) ODN) on hCG-induced progesterone production of isolated rat luteal cells in relation to cAMP, Ca(2+) and cycloheximide (CYX) were investigated. Antisense c-erbB(2) ODN inhibited hCG-induced progesterone production in a dose-dependent manner; and the percentage of luteal cells stained for c-erbB(2) protein was decreased. But nonsense tat ODN had no similar effect. The effect of dbcAMP was in contrast with that of antisense c-erbB(2) ODN, which suppressed the progesterone production and reduced the percentage of luteal cells stained for c-erbB(2) protein. On the other hand, both verapamil and CYX enhanced the inhibition of antisense c-erbB(2) ODN. The result of the present investigation suggests that cAMP, Ca(2+)-dependent pathway participates in the expression of protooncogene.