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Background: Endoplasmic reticulum (ER) stress, promoting lipid metabolism disorders and steatohepatitis, contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Hugan Qingzhi tablets (HQT) has a definite effect in the clinical treatment of NAFLD patients, but its mechanism is still unclear. This study aims to investigate the effects of HQT on ER stress in the liver tissues of NAFLD rats and explore the underlying mechanism., Methods: The NAFLD rat model was managed with high-fat diet (HFD) for 12weeks. HQT was administrated in a daily basis to the HFD groups. Biochemical markers, pro-inflammatory cytokines, liver histology were assayed to evaluate HQT effects in HFD-induced NAFLD rats. Furthermore, the expression of ER stress-related signal molecules including glucose regulating protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), p-PERK, eukaryotic translation initiation factor 2α (EIF2α), p-EIF2α, activating transcription factor 4 (ATF4), acetyl-coenzyme A-carboxylase (ACC), activating transcription factor (ATF6), and nuclear factor-kappa B-p65 (NF-κB-p65) were detected by western blot and/or qRT-PCR., Results: The histopathological characteristics and biochemical data indicated that HQT exhibited protective effects on HFD-induced NAFLD rats. Furthermore, it caused significant reduction in the expression of ERS markers, such as GRP78, PERK, p-PERK, and ATF6, and subsequently downregulated the expression of EIF2α, p-EIF2α ATF4, ACC, and NF-κB-p65., Conclusions: The results suggested that HQT has protective effect against hepatic steatosis and inflammation in NAFLD rats by attenuating ER stress, and the potential mechanism is through inhibition of PERK and ATF6 pathways., (© 2024. The Author(s).)

Shenhua tablet (SH), a formulation of traditional Chinese medicine, exerts renoprotective effect on chronic kidney diseases, and it has been found to restrain inflammation, but the mechanism is still unclear. Here, we explored the potential renoprotection of SH in mesangial proliferative glomerulonephritis (MsPGN) rat model induced by anti-Thy1 antibody. Administration of SH reduced urinary albumin/creatinine ratio (UACR) and significantly attenuated mesangial cell proliferation and renal inflammation. Notably, SH protected rats against renal inflammation, which was associated with decreasing macrophage infiltration and promoting macrophage anti-inflammatory activity. Network analysis combined with arrays identified the Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway as the main pathways of SH could target inflammation. Furthermore, it was confirmed that mesangial cell proliferation, which response to inflammation, were alleviated by ASS1 expression enhanced after SH administration both in vivo and in vitro. Collectively, SH has the beneficial on relieving the progression of MsPGN to alleviate inflammation and mesangial proliferation by inhibiting STAT3 phosphorylation and maintains the expression level of ASS1, might be an effective strategy for treating MsPGN., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Masson SAS.)

Jitongning tablet (JTNT) is a Traditional Chinese Medicine (TCM) prescription used for the treatment of Ankylosing spondylitis (AS). Currently, it is in phase II clinical trial (NCT03932019) for patients with active axial Spondyloarthritis (axSpA), showing great promise for the treatment of AS. However, the potential material basis and the underlying mechanisms for JTNT to treat AS remain elusive. Here, we performed UPLC-Q-TOF-MS to determine the in vivo metabolic profile of JTNT in rats and conducted in vivo studies including acetic acid-induced writhing, hot plate models, and collagen-induced arthritis (CIA) in rats to evaluate and validate the analgesic and anti-inflammatory effects of JTNT, two main symptoms for AS. Additionally, network pharmacology combined with molecular docking was performed to investigate the potential underlying mechanisms. As a result, a total of 116 xenobiotics were identified from the plasma, urine, and brain tissues of rats after oral administration of JTN extracts. Pharmacological evaluation revealed that fractions JTN-3 and JTN-4 exerted significant analgesic activities by reducing the number of writhes in an acetic acid-induced writhing mice model. JTN extract also exerted excellent therapeutic effects in the CIA model by ameliorating paw edema and decreasing systemic manifestation of inflammation and the level of circulating immune complex (CIC) and interferon γ (IFN-γ). Fractions of JTN extract, especially JTN-2 and JTN-4, on the other hand, ameliorated the secondary lesions caused by chicken type II collagen (CII) to a certain extent. Further, network pharmacology combined with molecular docking suggested crucial roles of inflammation and immune-related genes such as MAPK1, MAPK14, NOS3, and RELA in the treatment of AS by JTNT. In conclusion, our studies suggest that the isoquinoline and diterpenoid alkaloids from Corydalis Rhizoma and Aconiti Radix Cocta, along with coumarins from Angelicae Pubescentis Radix, may be the main bioactive components, and the AS treatment mechanism may mainly involve immune regulation of JTNT. These results help clarify the potential material basis and underlying mechanisms of JTNT for the treatment of AS, facilitating the broad application of this TCM in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jinshan Tang, Yi He and Xinsheng Yao reports financial support was provided by National Key Research and Development Program of China., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to describe the absolute oral bioavailability of the solid oral formulation of posaconazole and the impact of severe intestinal mucositis in haematology patients. This study also aimed to describe posaconazole protein binding in haematology patients., Methods: A pharmacokinetic study was performed of patients receiving induction chemotherapy or a haematopoietic cell transplantation who were randomized to receive 7 days of intravenous posaconazole therapy followed by 9 days of oral therapy, or vice versa. Patients received a posaconazole licensed dose until day 12, after which a reduced once-daily dose of 200 mg was given. At days 7, 12, and 16, blood samples were obtained for pharmacokinetic curves, and trough samples were collected on all other days. Total and unbound posaconazole pharmacokinetics were analyzed by population pharmacokinetic modelling. The presence of severe intestinal mucositis was assessed by plasma citrulline levels and analyzed as a binary covariate using 10 μmol/L as the cut-off. Monte Carlo simulations were performed to simulate posaconazole exposure at a steady state., Results: Twenty-three patients were included for analysis, with 581 total posaconazole concentrations and 91 paired unbound concentrations. Absolute bioavailability in the final model was estimated at 51.4% (percentage relative standard error (%RSE): 56.5) and 67.6% (%RSE: 75.0) in patients with and without severe intestinal mucositis, respectively. Posaconazole unbound fraction was estimated at 2.7% (%RSE: 3.9)., Discussion: Posaconazole bioavailability is reduced in haematological patients with severe intestinal mucositis, requiring an increase in oral posaconazole dose to 400 mg twice daily on day 1, followed by 400 mg once daily or a switch to intravenous therapy., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Abstract: Crushed oral tablets, when injected intravenously, may induce a foreign body granulomatous reaction in and around pulmonary arterioles, because of the presence of filler materials (excipients). This typically presents as shortness of breath in the context of pulmonary hypertension with arteriolar dilation and centrilobular nodules on imaging modalities. The constellation of findings may be overlooked or misdiagnosed by clinicians and pathologists, ultimately affecting patient care and postmortem assessment. We describe 5 patients with excipient lung disease that had antemortem chronic medical conditions that required a peripherally inserted catheter or port. All 5 patients had intravascular and perivascular deposition of polarizable foreign material within the pulmonary arteries. Foreign body granulomatosis as a result of intravenous drug use was not clinically suspected in any patient, and 2 of the 5 patients were misdiagnosed with mycobacterium infections. Pulmonary congestion, dyspnea, and symptoms of heart failure were noted in 3 patients and 2 had a history of upper arm deep vein thrombosis. We conclude that excipient lung disease may be underdiagnosed cause of dyspnea, pulmonary hypertension, and death in patients with a known history of intravenous drug use., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective This study aimed to determine the prevalence and endoscopic features of zinc acetate dihydrate tablet-associated gastric lesions. Methods We retrospectively examined the endoscopic features of 47 patients taking zinc acetate dihydrate tablets who underwent esophagogastroduodenoscopy. Results Gastric mucosal alterations, including redness, erosions, ulcers, and adhesion of the white coat, were observed in 29 of 47 patients (61.7%). Among patients with gastric lesions (group A), there was a significantly higher percentage of symptomatic patients in comparison to patients without lesions (group B) (65.5% vs. 22.2%; p<0.01). The background characteristics of the two groups did not differ to a statistically significant extent. On esophagogastroduodenoscopy, mucosal redness (n=27, 93.1%), erosions (n=26, 90.0%), adhesion of the white coat (n=25, 86.2%), and ulcers (n=9, 31.0%) were observed. None of the 19 patients who previously underwent esophagogastroduodenoscopy had gastric lesions before starting zinc acetate dihydrate. Esophagogastroduodenoscopy was performed after the cessation of zinc acetate dihydrate intake in six patients, and revealed the resolution of gastric lesions. Conclusion Gastric lesions were observed in 29 of 47 patients who were taking zinc acetate dihydrate tablets. The most common endoscopic findings were mucosal redness (93.1%), erosions (90.0%), adhesion of the white coat (86.2%), and ulcers (31.0%). Although the exact pathogenesis is uncertain, we believe that understanding the unique manifestations of this gastric lesion will help physicians manage adverse events in patients taking zinc acetate dihydrate tablets.