Correlations among the plasma concentrations of first-line anti-tuberculosis drugs and the physiological parameters influencing concentrations.

Background: The plasma concentrations of the four most commonly used first-line anti-tuberculosis (TB) drugs, isoniazid (INH), rifampicin (RMP), ethambutol (EMB), and pyrazinamide (PZA), are often not within the therapeutic range. Insufficient drug exposure could lead to drug resistance and treatment failure, while excessive drug levels may lead to adverse reactions. The purpose of this study was to identify the physiological parameters influencing anti-TB drug concentrations. Methods: A retrospective cohort study was conducted. The 2-h plasma concentrations of the four drugs were measured by using the high-performance liquid chromatography-tandem mass spectrometry method. Results: A total of 317 patients were included in the study. The proportions of patients with INH, RMP, EMB, and PZA concentrations within the therapeutic range were 24.3%, 31.5%, 27.8%, and 18.6%, respectively. There were positive associations between the concentrations of INH and PZA and RMP and EMB, but negative associations were observed between the concentrations of INH and RMP, INH and EMB, RMP and PZA, and EMB and PZA. In the multivariate analysis, the influencing factors of the INH concentration were the PZA concentration, total bile acid (TBA), serum potassium, dose, direct bilirubin, prealbumin (PA), and albumin; those of the RMP concentration were PZA and EMB concentrations, weight, α-l-fucosidase (AFU), drinking, and dose; those of the EMB concentration were the RMP and PZA concentrations, creatinine, TBA and indirect bilirubin; and those of the PZA concentration were INH, RMP and EMB concentrations, sex, weight, uric acid and drinking. Conclusion: The complex correlations between the concentrations of the four first-line anti-TB drugs lead to a major challenge in dose adjustment to maintain all drugs within the therapeutic window. Levels of TBA, PA, AFU, and serum potassium should also be considered when adjusting the dose of the four drugs.

Evaluation of Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis in Southwest China.

The purpose of this study was to determine the diagnostic efficacy of Xpert MTB/RIF assay for rapid diagnosis of Tuberculosis (TB) and detection of rifampicin (RIF) resistance in patients suspected of having EPTB, assessing it against traditional culture and drug susceptibility test (DST) by proportional method, and the ability to predict multidrug resistance TB by Xpert MTB/RIF assay. In this study, the Xpert MTB/RIF assay was applied to 1,614 extrapulmonary specimens. Compared with TB culture and Composite Reference Standard (CRS), the Xpert MTB/RIF assay had a high sensitivity and specificity for detection of EPTB. Depending on the culture method or CRS as the standard, sensitivity of the Xpert MTB/RIF assay for detection of MTB in pleural effusion, cerebrospinal fluid, thoracic drainage fluid and throat swabs specimens were lower than that of other specimens. According to the experimental results, we have reason to believe that Xpert MTB/RIF assay is a rapid and simple technique with high sensitivity and specificity for diagnosing EPTB and detecting drug resistance in variety of specimens. Xpert MTB/RIF assay combined with DST maybe identify more cases of multi-drug resistant tuberculosis (MDR-TB).

Metabolites Analysis on Water-Holding Capacity in Beef Longissimus lumborum Muscle during Postmortem Aging.

Currently, the metabolomic research on water-holding capacity (WHC) of beef during postmortem aging is still insufficient. In this paper, the kit method was adopted for energy metabolites testing, the ultra-high-performance liquid chromatography (UHPLC) system was used for sample separation, and the mass spectrometer was applied to collect the primary and secondary spectra of the samples. The results showed that lactic acid reached saturation at day 2 postmortem, while energy metabolites changed significantly within day 2 postmortem (p < 0.05). Based on these findings, it was suggested that the energy metabolism qualities of the beef had already achieved a largely stable state at around day 2 postmortem. Then, through metabolomic analysis, 25 compounds were differentially abundant at days 0, 0.5, 1, and 2 during postmortem aging. Within the period of day 0−2 postmortem, the purine metabolism in beef was relatively active until 0.5 d postmortem, while glycolysis metabolism remained active until day 2 postmortem. The functions of the identified metabolites contribute to a more detailed molecular view of the processes behind WHC and are a valuable resource for future investigations into the flavor of postmortem beef.

Application of real-time simultaneous amplification and testing method to accurately and rapidly detect extra-pulmonary tuberculosis.

BACKGROUND: This study aimed to establish and evaluate a simultaneous amplification and testing method for detection of extra-pulmonary tuberculosis (EPTB). METHODS: From January 2016 and December 2017 the pus or surgical excision from the lesions of inpatients admitted from Chongqing Public Health Treatment Center were collected. According to the clinical diagnosis, the samples were divided into two groups including EPTB (Group A) and other diseases excluded from tuberculosis diseases (Group B). Simultaneous detection of Mycobacterium tuberculosis (MTB) used Roche culture method, liquid culture method and simultaneous amplification and testing (SAT) method. The sensitivity and specificity of the SAT method were compared with culture methods and clinical diagnosis of EPTB. RESULTS: For 433 EPTB specimens and 49 non-TB specimens, the simultaneous amplification and testing tuberculosis (SAT-TB) results correlated with 80.5% (388/482 specimens) of the culture assay results. The sensitivity, specificity, and positive and negative predictive values of the SAT-TB test for the diagnosis of EPTB were 83.6, 79.4, 59.4, and 93.0%, respectively, compared to culture methods. Compared with the clinical diagnosis of patients, the sensitivity and specificity of the SAT-TB test were 41.6 and 100%, respectively, the cultures test were 29.3 and 98.0%. CONCLUSIONS: SAT test is a simple and rapid test with high specificity which may enhance the detection of EPTB. SAT-TB is a higher clinical diagnosis value for EPTB in clinical microbiology laboratories.

Involvement of erbB4 and tumor marker genes in renal carcinoma regulatory network.

BACKGROUND: Renal carcinoma is a common urologic tumor, and there is no ideal tumor marker for clinical diagnosis except for imaging diagnosis. This study aims to screen the serum tumor markers closely related with the benign and malignant of renal carcinoma out and chart out the regulatory network that involves renal carcinoma-related genes. METHODS: Based on 96 pathologically diagnosed renal cancer patients, factors strongly linked to renal carcinoma character were selected using Fisher discriminant analysis. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to manipulate function annotation of erbB4 and the selected genes and pathway analysis. RESULTS: Four essential tumor markers CYFRA21-1, CA125, VHL and HIF-1ß were successfully screened out. Using GO and KEGG databases, the regulatory network of renal cancer cell escaping apoptosis was charted out on the basis of erbB4 signaling pathway. CONCLUSION: Serum tumor marker genes play a certain part in the genesis and development of renal carcinoma. We preliminarily illustrated the molecular mechanism of these markers to predict tumor, laying a foundation for further exploration in renal carcinoma.