Model-based dosing optimization and therapeutic drug monitoring practices of teicoplanin in patients with complicated or non-complicated methicillin-resistant staphylococcus aureus infection.

AIMS: This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. METHODS: Nonlinear mixed-effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. RESULTS: A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non-complicated methicillin-resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. CONCLUSIONS: Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow-up therapeutic drug monitoring of teicoplanin at least once every week.

MiR-145 participates in the development of lupus nephritis by targeting CSF1 to regulate the JAK/STAT signaling pathway.

BACKGROUND: Lupus nephritis (LN) is a chronic autoimmune disease, leading to progressive renal dysfunction. MicroRNAs (miRNAs) contribute to LN pathophysiology. Nevertheless, the potential mechanisms of miR-145 in LN remain unclear. Here, we investigated the contribution of miR-145 to LN progression. METHODS: qRT-PCR analysis determined miR-145 and CSF1 expression. Western blot tested CSF1, JAK2, p-JAK2, STAT3, p-STAT3, cleaved caspase3, Bax and Bcl-2 expression. Dual luciferase reporter assay confirmed the interaction between miR-145 and CSF1. ELISA assay detected the secretion of inflammatory molecules. Flow cytometric analysis determined cell cycle and apoptosis. MTT was conducted to test cell viability. The LN mouse model was constructed for in vivo experiments. HE and Masson staining examined the kidney pathologic changes. RESULTS: MiR-145 was down-regulated in LN patients and LPS-induced HRMCS, whereas CSF1 was up-regulated. Moreover, miR-145 overexpression inhibited HRMCS cell apoptosis and inflammatory damage. Besides, miR-145 was found to directly target CSF1. Additionally, knockdown of CSF1 inhibited HRMCS cell apoptosis and inflammatory damage by inactivating the JAK/STAT signaling pathway. Furthermore, miR-145 inhibited inflammatory damage and cell apoptosis of HRMCS by down-regulating CSF1. Finally, we verified that miR-145 suppressed LN development in vivo. CONCLUSION: Our data reveals that miR-145 regulates LN progression via CSF1 mediated JAK/STAT signaling pathway, and miR-145 may be a new therapeutic target for LN treatment.

Social support and quality of life among rural family caregivers of persons with severe mental illness in Sichuan Province, China: mediating roles of care burden and loneliness.

OBJECTIVE: To explore the relationship between social support and quality of life (QoL) among family caregivers of persons with severe mental illness (SMI) and examine the mediating roles of care burden and loneliness. METHODS: A cross-sectional study was carried out between December 2017 and May 2018. A random sample of 256 family caregivers of persons with SMI in rural areas of Sichuan Province, China was recruited for participation. Survey data on socio-demographics, social support, care burden, loneliness, and QoL were collected via in-person interviews. Multiple linear regression analysis and structural equation modeling (SEM) were used to test the hypothesized relationships. RESULTS: The majority (72.7%) of family caregivers of persons with SMI in this study reported having low QoL. Social support was positively associated with QoL and negatively associated with care burden and loneliness. The findings suggested the mediating roles of care burden and loneliness on the association between social support and QoL. CONCLUSION: The hypothesized model was found to be a suitable model for predicting QoL among family caregivers of persons with SMI. The findings can help inform the design of future interventions aimed at enhancing social support, reducing care burden and loneliness, which may be helpful to improve caregivers' QoL. Future study is required to find a causal path to promote QoL among family caregivers of persons with SMI.