Latest ArticlesTo establish a method for determining the concentration of contezolid in human cerebro spinal fluid (CSF) using ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).
Linezolid as the internal standard (IS) and acetonitrile as the protein precipitant. Waters ACQUITY UPLC® BEH C18 (2.1 mm×50.0 mm, 1.7 μm) chromatographic column was used for separation, with a mobile phase of 0.1% formic acid aqueous solution-0.1% formic acid acetonitrile solution, gradient elution method, flow rate was 0.4 mL·min-1, column temperature was 40 ℃, automatic sampler temperature was 10 ℃, the analysis time was 4 minutes. Electrospray ion source, positive ion mode, and multi-reaction monitoring scanning mode were used. The monitoring and analysis ion pairs for contezolid were m/z 409.15→269.14, and the monitoring ion pairs for linezolid were m/z 338.14→195.10. The specificity, standard curve and lower limit of quantification (LLOQ), precision and recovery rate, matrix effect, residual effect, dilution effect and stability of the method were investigated.
The endogenous substances in CSF do not interfere with the determination of the analyte contezolid and the internal standard linezolid, and the method has good specificity. Satisfactory linearity was observed within the concentration range of 20-5 000 ng·mL-1 for contezolid in CSF, the calibration curve was y=8.97×10-4x+1.95×10-2 (r=0.999 1), and the LLOQ was 20 ng·mL-1. Precision of the intra-batch and inter-batch relative standard deviation (RSD)<15%, and the extraction recovery were 90.96%-98.71%. The average normalized matrix effect factor of the quality control CSF sample were 94.39%-100.25%. The RSD of dilution effect<15%. The CSF samples of contezolid were stored at room temperature, in the automatic sampler for 72 hours, -20 ℃ and -80 ℃ for 90 days, and subjected to repeated freezing and thawing three times, were stable with all of which the RSD<10%.
This method is high sensitivity, rapid, simple and accurate, which is very suitable for the therapeutic drug monitoring of contezolid in human CSF.
The active ingredient of WINREVAIR, sotatercept-csrk, is a recombinant activin receptor IIA-Fc (ActRIIA-Fc) fusion protein that improves pro-proliferation (ActRIIA/Smad2/3-mediated) and anti-proliferation (BMPRII/Smad1/5/8-mediated) signals, thereby regulating vascular proliferation. In March 2024, WINREVAIR was approved by the U.S. Food and Drug Administration for the treatment of pulmonary arterial hypertension (PAH) in adults. Clinical studies have shown that WINREVAIR can improve exercise capacity and reduce the incidence of all-cause death or clinical worsening of PAH by 84%. Common adverse drugreactions include headache, epistaxis, rash, etc.
Non-small cell lung cancer (NSCLC) constitutes the largest portion of lung cancer overall, with high incidence and mortality rates. Apoptosis, is a hot focus in the clinical treatment of NSCLC, its main pathways include the extrinsic death receptor pathway, intrinsic mitochondrial apoptosis pathway and endoplasmic reticulum stress pathway, collectively regulating the cellular apoptosis process. Traditional Chinese medicine (TCM) has significant efficacy in the treatment and prognosis of NSCLC, with advantages such as boosting the body’s resistance and less adverse drug reactions. Studies have shown that various individual Chinese herbal medicines and compound formulas can treat NSCLC through the apoptosis pathway, alleviating the adverse drug reaction of radiotherapy and chemotherapy. Based on this, this article summarizes recent domestic and international literature, focusing on apoptosis, to summarize the research progress of TCM in treating NSCLC by regulating apoptosis, aiming to provide reference for clinical treatment for NSCLC.
p38 mitogen-activated protein kinases (p38 MAPK) are involved in the regulation of osteosarcoma (OS) development. Therefore, this paper reviews the current research status of p38 MAPK signaling pathway in OS, mainly including the p38 MAPK signaling pathway regulates the biological behaviors of OS such as proliferation, migration, invasion, apoptosis, autophagy, iron death, angiogenesis and epithelial-mesenchymal transition (EMT), and non-coding RNAs and oxidative stress are involved in the development of OS through the modulation of p38 MAPK signaling pathway. reviewed to provide new ideas for finding the treatment of OS.
Excessive fat accumulation, viral infections and sustained inflammatory responses caused by non-alcoholic and alcoholic factors can contribute to liver inflammation, fibrosis and carcinogenesis, promoting the development of chronic liver disease. Gaining an in-depth understanding of the etiologic factors and underlying mechanisms that lead to chronic liver disease can help identify potential therapeutic targets for targeted therapy. Lactate, as an important substance in hepatic metabolism, has been found to be involved in the process of chronic liver disease through various pathways, and this review will provide a useful reference for the prevention and treatment of chronic liver disease.
Drug-induced liver injury (DILI) is a common adverse drug reactions in clinical practice, with complex pathophysiological process, the pathogenesis has not been fully elucidated, and lack of objective and specific diagnostic methods and treatment, so the prevention and treatment of DILI has attracted extensive attention from scholars. In recent years, the intestinal flora has become a research hotspot in the field of DILI, and the intestinal flora causes or exacerbates DILI by damaging the intestinal mucosal barrier, affecting the metabolites of the intestinal flora and mediating the immune response, and the gut-liver axis is an important pathway for the intestinal flora to participate in the occurrence of DILI, regulating intestinal flora is practicable in the treatment of DILI. This article reviews the characteristics of intestinal flora in DILI patients, and to explore the possible mechanisms of intestinal flora participating in the pathogenesis of DILI through the gut-liver axis, summarizes the latest progress of intervention in the treatment of DILI by intestinal flora, in order to provide references for the screening of the diagnostic targets of DILI and its prevention and treatment from the perspective of intestinal flora.
Hypertensive nephropathy is one of the common chronic kidney diseases in China, the morbidity and mortality are increasing year by year, which seriously endangers the physical and mental health of patients. Traditional Chinese medicine believes that human is an organic whole, the five viscera and six organs are closely related in physiology and pathology, based on the theory of “holistic concept”, the application of Chinese medicine in the treatment of hypertensive nephropathy can effectively improve kidney function and reduce the occurrence of adverse reactions. Therefore, based on the theory of “five viscera in one”, this paper summarizes the etiology and pathogenesis of hypertensive nephropathy and the treatment of hypertensive nephropathy from the five aspects of liver, heart, spleen, lung and kidney, aiming to provide new ideas for the prevention and treatment of kidney disease by traditional Chinese medicine.
Diabetic kidney disease (DKD) is one of the common microvascular complications of diabetes mellitus, and it has become the main cause of chronic kidney disease and end stage renal disease. Traditional Chinese medicine can delay the progress of DKD by inhibiting oxidative stress, improving renal tissue damage, restoring renal function. This paper will summarize the relationship between oxidative stress and DKD and the prevention and treatment of DKD by traditional Chinese medicine, so as to provide reference for clinical drug application, basic research and new drug research and development of DKD.
The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway plays a crucial role in the regulation of renal fibrosis by participating in inflammatory response, oxidative stress and autophagy. Paeoniflorin exhibits remarkable efficacy in treating myocardial and liver fibrosis. This article provides a comprehensive review on the research progress of paeoniflora in preventing and treating renal fibrosis through modulation of the PI3K/Akt/mTOR signaling pathway, offering novel insights for traditional Chinese medicine-based approaches to prevent and treat renal fibrosis.
Hemophilia is a rare monogenic inherited coagulation factor deficiency disease, which begins in early childhood, and severe patients often have a history of spontaneous bleeding or joint muscle bleeding, requiring long-term frequent transfusion of clotting factor. This article reviews the clinical development process of bispecific antibody drug EMICIZUMAB and two gene therapies ROCTAVIAN and HEMGENIX for the corresponding hemophilia subtypes, so as to summarize the strategies for rare disease drug development and the key elements of gene therapy drug development, and to provide reference for the development of similar drugs in similar indications in the future.
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