Clinical features and risk factors of pulmonary tuberculosis complicated with pulmonary aspergillosis.

OBJECTIVE: This study was carried out to explore the clinical features and risk factors of pulmonary tuberculosis complicated with pulmonary aspergillosis. PATIENTS AND METHODS: Through a retrospective analysis of 3,000 patients with pulmonary tuberculosis history or active pulmonary tuberculosis complicated with pulmonary aspergillosis in the inpatient department of pulmonary tuberculosis in Shandong Provincial Public Health Clinical Center from January 2017 to January 2021, 70 cases of pulmonary aspergillosis were selected and diagnosed. In addition, 70 patients with pulmonary tuberculosis without other fungal infections in the same period were randomly selected as the control group. The risk factors of pulmonary tuberculosis complicated with pulmonary aspergillosis were analyzed by multi-factor logistic analysis, and the clinical characteristics of pulmonary tuberculosis complicated with pulmonary aspergillosis were analyzed by collecting the basic information of patients, drug use of pulmonary tuberculosis, imaging characteristics, past medical history, and test indicators. RESULTS: Univariate analysis showed that the single risk factors of pulmonary tuberculosis complicated with pulmonary aspergillosis were: the types of pulmonary tuberculosis (initial diagnosis or previous reexamination), hormone application time, antibiotic application time (rifampicin), hemoptysis/sputum blood, C-reactive protein, and pulmonary cavity were significantly correlated with pulmonary tuberculosis complicated with pulmonary aspergillosis (p-value <0.05). The proportion of patients with pulmonary tuberculosis complicated with pulmonary aspergillosis was higher than that of patients with simple pulmonary tuberculosis in the follow-up of pulmonary tuberculosis, the time of antibiotics application ≥ 1 month, the time of hormone application ≥ 1 week and C-reactive protein. The incidence of hemoptysis/blood in sputum in the clinical symptoms of pulmonary aspergillosis group (24/70) was higher than that of simple pulmonary tuberculosis group (20/70), and the difference was statistically significant (p-value < 0.05). Multivariate logistic regression analysis showed that there were significant differences between the two groups in the two indexes of "hormone application time ≥ 1 week" and "antibiotic application time ≥ 1 month" (p-value < 0.05). CONCLUSIONS: Hemoptysis/blood in sputum can be considered as the main clinical feature of pulmonary tuberculosis complicated with pulmonary aspergillosis. The main risk factors for pulmonary tuberculosis complicated with pulmonary aspergillosis were the application time of antibiotics ≥ 1 month and the application time of hormones ≥ 1 week.

The ERK-ZEB1 pathway mediates epithelial-mesenchymal transition in pemetrexed resistant lung cancer cells with suppression by vinca alkaloids.

High thymidylate synthase (TS) level in cancer tissue is considered to result in resistance to pemetrexed therapy for advanced stages of nonsquamous non-small cell lung cancers. To further investigate the mechanism of pemetrexed resistance and potential prognostic outcomes in lung cancer, we established pemetrexed-resistant lung adenocarcinoma cell sublines from CL1 harboring a mutated TP53 gene (R248W) and A549 harboring wild-type TP53. We found the TS expression is upregulated in both pemetrexed-resistant sublines and the reduced TS level achieved through shRNA inhibition resulted in higher pemetrexed sensitivity. We also demonstrated that the acquisitions of pemetrexed resistance enhances epithelial-mesenchymal transition (EMT) in vivo with a mice animal model and in vitro with CL1 and A549 sublines, which was associated with upregulation of ZEB1 which, in turn, downregulates E-cadherin and upregulates fibronectin. When ERK1/2 phosphorylation was reduced by an inhibitor (U0126) or siRNA inhibition, both pemetrexed-resistant sublines reduced their migration and invasion abilities. Therefore, the ERK-mediated pathways induce apoptosis with pemetrexed treatment, and may in turn mediate EMT when cancer cells are resistant to pemetrexed. We further demonstrated that the growth of pemetrexed-resistant tumors could be inhibited by vinblastine in vivo and vincristine in vitro. Our data indicate that pemetrexed resistance could be relieved by non-cross-resistant chemotherapeutic drugs such as vinca alkaloids and might be independent to TP53 status. Furthermore, the phosphorylation of ERK was reduced by vincristine. This finding provides a new insight for overcoming pemetrexed resistance and metastasis by application of vinca alkaloids.

Comparative bioavailability of rifampicin and isoniazid in fixed-dose combinations and single-drug formulations.

SETTING: The bioavailability of rifampicin (RMP) decreases by ∼30% on interaction with isoniazid (INH) in stomach acid conditions, which can result in the development of drug resistance and treatment failure. OBJECTIVE: To compare the bioavailability in healthy volunteers of five anti-tuberculosis fixed-drug combinations (FDCs) used in China (formulations A-E) containing RMP and INH against single-drug formulations taken as reference. DESIGN: Two- or three-period, two- or three-sequence crossover study of drugs. RESULT: Only RMP formulation E passed the bioequivalence criteria, with 90% confidence intervals for the log-transformed ratios of AUC0₋24, AUC0₋∞, and Cmax of respectively 89.9-103.7, 89.6-102.2 and 87.7-107.9. For INH, formulations A, B, C and D passed the bioequivalence test, but not product E, where the 90%CIs of the log-transformed ratios of AUC0₋24, AUC0₋∞, and Cmax were respectively 85.2-100.7, 85.2-100.7 and 73.8-100.9. CONCLUSION: According to the results of the bioequivalence analysis carried out in this study, RMP formulations A, B, C and D were not within the acceptable range and only formulation E passed the bioequivalence criteria of 80-125%. In comparison, four-test INH formulations (A, B, C and D) were bioequivalent to the corresponding single-drug formulation, while product E failed in the bioequivalence criteria.

Dynamic characteristics of long-wavelength quantum dot vertical-cavity surface-emitting lasers with light injection.

This investigation experimentally demonstrates the dynamic characteristics of quantum dot vertical-cavity surface-emitting lasers (QD VCSEL) without and with light injection. The QD VCSEL is fully doped structure on GaAs substrate and operates in the 1.3 mum optical communication wavelength. The eye diagram, frequency response, and intermodulation distortion are presented. We also demonstrate that the frequency response enhancement by light injection technique allows us to improve the performance of subcarrier multiplexed system.

Tunable slow light device using quantum dot semiconductor laser.

This investigation experimentally demonstrates a tunable slow light device using a quantum dot (QD) semiconductor laser. The QD semiconductor laser at 1.3 mum fabricated on a GaAs substrate is grown by molecular beam epitaxy. Tunable slow light can be achieved by adjusting the bias current and wavelength detuning. The slow light device operated under probe signal from 5 to 10 GHz is presented. Moreover, we also demonstrate that the tunable slow light device can be used in a subcarrier multiplexed system.

Translation of Pseudomonas aeruginosa bacteriophage PP7 RNA by a cell-free amino acid incorporating system from Escherichia coli.

We have compared the activities of the RNA genomes of Pseudomonas aeruginosa phage PP7 and coliphages Qbeta and f2 in a cell-free amino acid incorporating system derived from Escherichia coli. The rate of incorporation of [(14)C]leucine in the PP7 RNA-directed system is greater than in the systems directed by either Qbeta or f2 RNA. The response to changes in phage RNA concentrations is similar in all the systems, reaching a saturation level at 0.75 to 1.0 mg of RNA per ml of reaction mixture. Analysis of complete reaction mixtures of the PP7 RNA and of the Qbeta RNA systems by sucrose gradient centrifugation shows generally similar patterns for both RNAs. The principal differences are that in the PP7 system a slightly higher percentage of RNA forms ribosome complexes and that the polysomes are somewhat smaller. PP7 RNA is also degraded more extensively during the reaction than is Qbeta RNA. Analysis of the products of the reactions by acrylamide gel electrophoresis shows that PP7 coat protein is the only identifiable product of the PP7 RNA-directed system, suggesting that only the coat protein cistron is translated by E. coli ribosomes.