Qi Huang

Background: There are significant interindividual variations in voriconazole (VCZ) blood concentrations, which affect both treatment efficacy and safety. Objective: Our goal is to identify the factors influencing VCZ trough concentrations and provide new evidence for individualized dosing. Methods: A total of 281 hospitalized patients receiving VCZ were enrolled. Demographic, liver and kidney function, C-reactive protein (CRP) and other clinical data were collected. Trough concentrations were determined using HPLC. Multivariate linear regression and ordinal logistic regression were employed to identify influencing factors, with predictive performance assessed by ROC curves. Results: CRP is a significant positive predictor of VCZ trough concentration (B = 0.010, p = 0.006), demonstrating the strongest predictive capability for elevated trough levels (>5 μg/mL) (AUC = 0.8864, p < 0.0001), outperforming conventional liver function indicators such as total bile acids (AUC = 0.6326). Loading dose also showed a significant correlation with increased trough concentration (B = 0.973, p = 0.007) and elevated the risk of supratherapeutic levels (OR = 0.430, p = 0.006). Additionally, weight, albumin, platelet count, and concomitant administration of pantoprazole or dexamethasone were identified as independent influencing factors. Conclusion: The high variability in VCZ trough concentrations may be partially attributed to factors such as weight, loading dose, liver function, inflammation and concomitant medications. Although loading doses enable rapid efficacy, they increase the risk of supratherapeutic concentrations. Patients in the high-CRP group are more likely to exceed 5.0 μg/mL, demonstrating the best discriminative ability for predicting excessively high concentrations. These findings provide new evidence for VCZ dose optimization.

Triptolide, a bioactive triepoxide diterpenoid extracted from Tripterygium wilfordii Hook. f., has demonstrated broad pharmacological activities and significant toxicities. Mechanistically, triptolide has exerted therapeutic effects by regulating programmed cell death (PCD) through multiple pathways; however, its toxic reactions have been closely associated with this process. This review systematically summarizes the molecular mechanisms by which triptolide regulated various forms of PCD and its application progress in disease treatment, including apoptosis, autophagy, pyroptosis, ferroptosis, cuproptosis, necroptosis, and PANoptosis. A plethora of extant studies have revealed that triptolide exerted a regulatory effect on the PCD networks by intervening in multiple important signaling pathways and their key signaling nodes. Nevertheless, due to its poor target specificity, triptolide has resulted in multi-organ toxicities, which has in turn limited its clinical translation. Nano-delivery systems have explored as a potential strategy to mitigate the toxicity and improve the efficacy of triptolide by enhancing its tissue targeting (Specific nanocarriers can increase LD ₅₀ from 0.48 to 0.88 mg/kg). Furthermore, key pharmacodynamic evidences from triptolide’s current clinical studies are limited, necessitating the elucidation of precise target sites and the advancement of standardized clinical trials. This review systematically integrates the pleiotropic pharmacological activities and multiple-organ toxicities of triptolide from a PCD perspective, providing novel insights and theoretical references for overcoming its clinical translation barriers. Graphical Abstract

Spiroleiferthione A (1), with a 2-thiohydantoin a heterocyclic spiro skeleton, and oleiferthione A (2), an imidazole-2-thione derivative, were isolated from the aqueous extract of Moringa oleifera Lam. seeds. The unprecedented structures of 1 and 2 were elucidated by extensive spectroscopic data, X-ray diffraction, and gauge-independent atomic orbital (GIAO) NMR calculation, as well as electronic circular dichroism (ECD) calculation. The structures of 1 and 2 were determined to be (5R,7R,8S)-8-hydroxy-3-(4′-hydroxybenzyl)-7-methyl-2-thioxo-6-oxa-1, 3-diazaspiro [4.4] nonan-4-one, and 1-(4′-hydroxybenzyl)-4,5-dimethyl-1,3-dihydro-2H-imidazole-2-thione, respectively. Biosynthetic pathways for 1 and 2 have been proposed. Compounds 1 and 2 are considered to have originated from isothiocyanate and then undergone a series of oxidation and cyclization reactions to form 1 and 2. Compounds 1 and 2 demonstrated weak inhibition rates of NO production, 42.81 ± 1.56% and 33.53 ± 2.34%, respectively, at a concentration of 50 μM. Additionally, Spiroleiferthione A demonstrated moderate inhibitory activity against high glucose-induced human renal mesangial cell proliferation in a dosage-dependent manner. A wider range of biological activities, and the diabetic nephropathy protective activity of Compound 1 in vivo and its mechanism of action, need further investigation after the sufficient enrichment of Compound 1 or total synthesis.

A considerable number of researches compared the effectiveness and safety different antibiotics for a disease caused by MRSA. However, comprehensive evaluated antibiotic therapeutic different diseases caused by MRSA is lacking. The network meta-analysis (NMA) comprehensively compared the effectiveness and safety of linezolid, teicoplanin, daptomycin, and tigecycline with vancomycin in treating methicillin-resistant Staphylococcus aureus (MRSA)-caused diseases. PubMed, Embase, Web of Science, Cochrane Library, CNKI, and Wan-fang databases were searched for studies until Sep 28, 2021. All eligible randomized controlled trials of five antibiotics were included in the NMA, and their effectiveness and safety were compared in various MRSA-attributed diseases. The dichotomous variables adopted for the odds ratio (OR) and the surface under the cumulative ranking (SUCRA) to evaluate the incidence rate. The study was performed using Rev Man 5.4 and STATA 16.0 software. SUCRA analysis revealed the superiority of linezolid to other antibiotics in total effectiveness rate (98.9%), microbial killing rate (99.6%), and total nephrotoxicity (17.8%). Regarding safety, the total adverse reaction rate of vancomycin was inferior to teicoplanin (OR 0.49, 95% CI 0.30–0.80). Vancomycin total hepatotoxicity was inferior to linezolid (OR 0.36, 95% CI 0.18–0.73) and tigecycline (OR 0.15, 95% CI 0.03–0.66), and it was also inferior to linezolid (OR 0.33, 95% CI 0.24–0.47) and teicoplanin (OR 0.35, 95% CI 0.18–0.69) in total nephrotoxicity. Linezolid had a higher risk of thrombocytopenia than teicoplanin (OR 4.24, 95% CI 1.26–14.24) and vancomycin (OR 2.14, 95% CI 1.17–3.90). Moreover, linezolid exhibited higher effectiveness in pneumonia compared to vancomycin (OR 2.06, 95% CI 1.58–2.69) and teicoplanin (OR 1.67, 95% CI 1.06–2.62). For skin and soft-tissue infections, linezolid showed superior effectiveness to vancomycin (OR 1.62, 95% CI 1.20–2.18). Regarding the microbial killing rate, vancomycin was inferior to linezolid in pneumonia (OR 0.38, 95% CI 0.29–0.49), skin soft-tissue infection (OR 0.41, 95% CI 0.21–0.79), and other infections (OR 0.40, 95% CI 0.20–0.83). And teicoplanin was inferior to linezolid in treating pneumonia (OR 0.51, 95% CI 0.33–0.81) and other infections (OR 0.39, 95% CI 0.18–0.86). The present research suggest that linezolid may be a better option for treating MRSA-caused diseases. However, caution is warranted owing to linezolid-associated thrombocytopenia.

Out of the global outbreak of COVID-19, clinical pharmaceutical therapeutic analytical-teaching laboratories underwent an increasing number of digitally-led teaching research. A teaching system working online and offline to monitor medicinal drugs was explored and established using a clinical pharmaceutical therapy through a drug concentration monitoring laboratory within a comprehensive tertiary hospital. Meanwhile, laboratory access training and standards of laboratory biosafety management system were also strictly implemented, improving the technical operation and daily management. Moreover, a new, significant, and efficient teaching mode was set up based on vocational training needs for efficient and professional learning. The learning results are enforced to have dynamic checks accomplished using stage-oriented assessment. Moreover, the questionnaire survey results, especially during independent learning ability and laboratory skills training, reveal that teachers and students have commented positively on the new teaching mode. Hereon, a clinical pharmaceutical teaching system during the Post-Epidemic Era was elaborated to provide a unique teaching mode and experience dedicated to teaching and scientific research in clinical therapeutic drug monitoring laboratory.

Two new chromone derivatives (1 and 2), and two known compounds (3 and 4) were isolated from the rhizosphere soil fungus Ilyonectria robusta. Their planar structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Additionally, all the isolated compounds were evaluated for their antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli, but no obvious activity was observed at a concentration of 128 μg/mL. Graphical Abstract

Objectives: Moringa oleifera (M. oleifera) Lam (Moringaceae) is a perennial plant broadly used in South Asia and Africa as a traditional folk medicine to treat many ailments such as paralysis, helminthiasis, sores and skin infections. The review provides a critical and comprehensive evaluation of the botany, traditional uses, phytochemistry, pharmacology, toxicity, agricultural economy and dietary benefit of M. oleifera and its future perspectives. Key findings: In this review, the entire plant of M. oleifera, containing diverse phytochemicals, is summarized. The 163 chemical components, included flavonoids, carbamates, glucosinolates, phenols, and so on with various bioactivities, such as anti-tumour, antioxidant, anti-inflammatory, and so on. Additionally, M. oleifera is toxic at certain doses; and overuse can cause genotoxicity. Summary: Although M. oleifera has been widely used in traditional medicine, the pharmacological studies that have been conducted so far are not sufficient for its use in the setting of evidence-based medicine. Little relevant data from clinical trials of M. oleifera have been reported. The majority of studies of its constituents, such as carbamates and glucosinolates, have been conducted only in vitro. Owing to a lack of available data, the pharmacology, toxicity, agricultural economy and dietary benefit of its constituents and extracts require further evaluation.

Diabetic nephropathy (DN) is a common complication in patients with diabetes and a leading cause of mortality. The management of DN in the clinic still remains a challenge. Therefore, the identification of novel compounds for DN treatment and their characterization in preclinical DN models are crucial. Isoeucommin A is a lignan compound isolated from Eucommia ulmoides Oliv, which has not been studied in detail. Our aim was to investigate the effect of Isoeucommin A in DN and to elucidate the molecular mechanisms though which Isoeucommin A acts in vitro and in vivo. We first isolated and purified Isoeucommin A by microporous resin column chromatography and studied the mass spectrogram, as well as the structure of Isoeucommin A, by high‐resolution electrospray ionization mass spectroscopy and NMR, respectively. We further established an in vivo rat DN model and measured the changes of blood glucose, body weight, kidney index (KI), blood urea nitrogen, creatinine (CRE), glutathione, malondialdehyde (MDA), SOD, albumin (ALB) and urinary ALB to CRE ratios on treatment with Isoeucommin A. In addition, we measured SOD, MDA, glycogen synthase kinase‐3β (GSK‐3β), phosphorylated (p)‐GSK‐3β, nuclear factor erythroid‐derived 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) levels by quantitative real‐time PCR and western blot, and estimated cell viability by a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide assay. After Isoeucommin A treatment, body weight, as well as SOD, glutathione, HO‐1 and Nrf2 expression levels, in DN rats increased in a dose‐dependent manner. In contrast, the levels of blood glucose, KI, blood urea nitrogen, CRE, urinary ALB to CRE ratio, tumor necrosis factor‐α, interleukin‐1β, interleukin‐6 and MDA decreased significantly. In addition, Isoeucommin A protected H₂O₂‐stimulated renal tubular epithelial cells from oxidative stress and activated the Nrf2/HO‐1 signaling pathway in high‐glucose‐stimulated human renal mesangial cells. In conclusion, Isoeucommin A could alleviate inflammation and oxidative stress in in vitro and in vivo DN models and thus attenuate kidney injury by activating the Nrf2/HO‐1 signaling pathway. Isoeucommin A could have the potential to be used as an effective drug for the treatment of DN.