To determine the safety and efficacy of bedaquiline for Chinese patients with multidrug-resistant tuberculosis (MDR-TB) based on serum concentration monitoring and to identify factors associated with QTc prolongation occurring during treatment. Data were collected from 35 patients who received treatment regimens containing bedaquiline for MDR-TB from May 2018 to December 2020. Blood samples were collected, and serum concentrations of bedaquiline were measured using high-performance liquid chromatography-mass spectrometry. After completing the 24-week bedaquiline treatment course, 80.0% of the patients' sputum cultures turned negative. The median time to sputum culture conversion was 75.5 days (interquartile range 52-126 days). The mean serum concentration of bedaquiline was 0.586 ± 0.288 µg/ml during treatment and 0.205 ± 0.145 µg/ml at 16 weeks after bedaquiline discontinuation. Bedaquiline remained detectable 52 weeks after discontinuation. Combination with clofazimine during bedaquiline treatment significantly increased cardiac QTc prolongation. When QTc prolongation occurred, serum potassium levels decreased by 10.71% from baseline, while serum sodium levels increased by 1.07% from baseline. Good treatment outcomes were obtained with bedaquiline treatment in Chinese patients with MDR-TB. Combination with clofazimine increased the risk of QTc prolongation. Serum electrolytes (potassium and sodium) should be measured regularly during treatment of MDR-TB with regimens containing bedaquiline.

Background: Gliomas are characterized by high mortality rates and resistance. Even with conventional chemotherapy the prognosis of glioblastoma remains poor. Many medications are not optimally effective due to limited bioavailability. The bioavailability of medicine can be enhanced by borneol, a monoterpenoid substance. In this study, we investigated the effect of borneol, a commonly used Chinese medicine, on chemosensitivity in C6 glioma and U251 human glioma cell lines and elucidated its therapeutic molecular targets. Methods: The chemosensitivity-inducing effects of borneol in C6 and U251 cells were examined using CCK8 and clonal formation assays. The mechanism underlying the effect of borneol was evaluated through immunohistochemistry and western blotting assays. Further, the number of autophagosomes was determined via transmission electron microscopy. Finally, the chemical sensitization effect of borneol was evaluated in SD rats after C6 orthotopic tumor transplantation. Results: Borneol increased cytotoxicity in C6 and U251 cells in response to temozolomide (TMZ). In addition, through transmission electron microscopy, western blotting, and immunohistochemical tests, we found that borneol combined with TMZ significantly increased the level of autophagy and that hypoxia inducible factor-1(HIF-1α) is a candidate target through which borneol enhances the cytotoxic effect of TMZ. Borneol’s ability to enhance HIF-1α degradation was counteracted following the administration of autophagy inhibitors. In vivo, borneol treatment was found to enhance the anticancer effect of TMZ and delay tumor progression, and this effect was closely related to its ability to promote the autophagic degradation of HIF-1α. Conclusions: HIF-1α might be a valid therapeutic target of borneol, which can be potentially applied as a chemosensitizing drug used for glioma treatment.

Multidrug-resistant tuberculosis (MDR-TB) remains a main global health concern as there is no comprehensive therapeutic intervention yet and numerous adverse effects follow the therapeutic process. In recent years, linezolid has been frequently used for treating MDR-TB. However, peripheral neuropathy associated with linezolid has reduced patient compliance. The current study explored the mechanism underlying linezolid-induced peripheral neuropathy in MDR-TB. Autophagy plays a neuroprotective role against peripheral nerve injury. We hypothesized that autophagy might also play a neuroprotective role against linezolid-induced peripheral neuropathy. In this study, we collected 12 questionnaires from MDR-TB patients in our hospital, and 10 of them developed linezolid-induced pain. The pain is mainly concentrated in the feet and accompanied by numbness. Subsequently, we used Sprague-Dawley (SD) rats and Schwann cells (SCs) to explore the mechanism. We found that linezolid causes a sparse arrangement of sciatic nerve tissue with associated loss of neurons, myelin sheaths, and down-regulation of LC3B expression. These results were also confirmed by in vitro experiments, showing that linezolid inhibited the proliferation of SCs. And the expression of P-AKT and P62 was elevated, and the expression of LC3B declined compared with the control group. Moreover, chloroquine (CQ), an autophagy inhibitor, also exhibited experimental results similar to linezolid. In summary, we conclude that linezolid-induced peripheral neuropathy is associated with the inhibition of autophagy flux.

Isoniazid (INH) plays an important role in prevention and treatment of tuberculosis (TB). However, large pharmacokinetic (PK) variations are observed in patients receiving standard INH dosages. Con...