Nine months of bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine chemotherapy for rifampicin/multidrug-resistant tuberculosis: a multicenter, randomized, open-label non-inferiority trial in China.

BACKGROUND: We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. METHODS: This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. RESULTS: Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). CONCLUSIONS: The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

ARMCX3 regulates ROS signaling, affects neural differentiation and inflammatory microenvironment in dental pulp stem cells.

Background: The neural differentiation of dental pulp stem cells (DPSCs) exhibits great potential in the treatment of dental pulp repair and neurodegenerative diseases. However, the precise molecular mechanisms underlying this process remain unclear. This study was designed to reveal the roles and regulatory mechanisms of the armadillo repeat-containing X-linked 3 (ARMCX3) in neural differentiation and inflammatory microenvironment in human DPSCs (hDPSCs). Methods: We treated hDPSCs with porphyromonas gingivalis lipopolysaccharide (Pg-LPS) to simulate the inflammatory microenvironment. Then the lentiviral vectors were introduced to construct stable cell lines with ARMCX3 knockdown or overexpression. The expression of neural-specific markers, ARMCX3 and inflammation factors were estimated by immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) assays. Additionally, we used IF assays and specific kits to investigate the regulatory role of ARMCX3 on reactive oxygen species (ROS) signaling. Moreover, a ROS inhibitor was utilized to verify whether ROS inhibition reversed the effects of ARMCX3 in Pg-LPS-treated hDPSCs. Results: This work illustrated that Pg-LPS treatment significantly enhanced ARMCX3 expression and inflammatory response, and inhibited neural differentiation in hDPSCs. ARMCX3 knockdown effectively accelerated neural differentiation and controlled inflammatory cytokines at a lower level in hDPSCs in the presence of Pg-LPS. Additionally, knockdown of ARMCX3 notably reduced ROS production and ROS inhibition effectively eliminated the roles of ARMCX3 overexpression in hDPSCs. Besides, all results were proved to be statistically significant. Conclusion: This investigation proved that ARMCX3 affected neural differentiation and inflammation microenvironment in hDPSCs at least partly by mediating ROS signal. These findings provided a new perspective on the mechanism of neural differentiation of hDPSCs and help to better explore the therapeutic schedule of pulpitis and neurodegenerative diseases.

Research progress on pharmacological effects and bioavailability of berberine.

Berberine (BBR), a benzylisoquinoline alkaloid obtained from natural medicines such as coptidis rhizoma, has a wide range of pharmacological activities such as protecting the nervous system, protecting the cardiovascular system, anti-inflammatory, antidiabetic, antihyperlipidemic, antitumor, antibacterial, and antidiarrheal. However, factors such as poor solubility, low permeability, P-glycoprotein (P-gp) efflux, and hepatic-intestinal metabolism result in BBR having a low bioavailability (< 1%), which restricts its application in clinical settings. Therefore, improving its bioavailability is a prerequisite for its clinical applications. This review summarizes the various pharmacological effects of BBR and analyzes the main reasons for its poor bioavailability. It introduces methods to improve the bioavailability of BBR through the use of absorption enhancers and P-gp inhibitors, structural modification of BBR, and preparation of BBR salts and cocrystals as well as the development of new formulations and focuses on the bioavailability study of the new formulations of BBR. The research of BBR was also prospected in order to provide reference for the further research of BBR.

Efficacy of Periodontal Endodontics Combined with Diode Laser (DL) Therapy on Severe Periodontitis.

Background: For a long time, the impact of severe periodontitis on the pulp has been the focus of periodontal clinical research. Whether the teeth with severe periodontitis should be treated with pulp has also become the focus of clinical research. Aims: To explore the effect of periodontal endodontic therapy combined with DL therapy on severe periodontitis. Materials and Methods: The clinical data of 100 patients with severe periodontitis from January 2020 to July 2022 were selected and included in the retrospective study. According to the different retrieval treatment methods, they were divided into the control group and the treatment group with 50 cases in each group. The control group received periodontal endodontic treatment, and the treatment group received DL treatment on the basis of the control group. The differences in periodontal probing depth (PD), toothache degree, bleeding index (BI), inflammatory factors, plaque index (PLI), and attachment loss (AL) between the two groups were compared and analyzed. Results: After 3 months of treatment, the bleeding index (BI), plaque index (PLI), and periodontal probing depth (PD) of the treatment group were significantly lower than those of the control group, and the difference was statistically significant (P < 0.05). The attachment loss (AL) of the group was not significantly different from that of the control group (P > 0.05). Before treatment, there was no significant difference in the levels of inflammatory factors between the two groups (P > 0.05). After 3 months of treatment, the levels of IL-6 and CRP in the treatment group were significantly lower than those in the control group, and the difference was statistically significant (P < 0.05). Before treatment, there was no significant difference in the levels of inflammatory factors between the two groups (P > 0.05). After 3 days of treatment, the VAS score of the treatment group was significantly lower than that of the control group, and the difference was statistically significant (P < 0.05).After treatment, there were no complications during follow-up in the two groups. Conclusion: The application of DL treatment has a significant effect, which can promote the healing of periodontal tissue, reduce the depth of periodontal pockets, and reduce the degree of toothache, thereby providing a reference for clinical treatment.

Spectral study of the interaction between 2-pyridinecarbaldehyde-p-phenyldihydrazone and ferric iron and its analytical application.

The synthesis and spectral characterization of a schiff base, 2-pyridinecarbaldehyde-p-phenylenedihydrazone (short for 2PC-PPH), were described. It was found that ferric ion (Fe(3+)) could selectively quench the fluorescence of 2PC-PPH, whereas many other metal ions, such as Mn(2+), Zn(2+), Cu(2+), K(+), Al(3+), Ca(2+), Ni(2+), Co(2+), Cr(3+) and Fe(2+), could not quench its fluorescence. Based on this, a sensitive method for ferric ion selective detection was established. Under the optimum conditions, the decreasing fluorescence intensity of 2PC-PPH is proportional to the concentration of Fe(3+) within the range of 6.0×10(-7)-1.0×10(-5) mol L(-1). The detection limit (3σ) for Fe(3+) determination is 3.6×10(-7) mol L(-1). The proposed method was successfully applied to determine iron in tea and milk powder.