Rationale: Immune checkpoint inhibitors, particularly programmed cell death protein 1 (PD-1) blockers, have transformed cancer therapy but can induce immune-related endocrine toxicities. Severe involvement of multiple endocrine axes, including dual pituitary dysfunction, is rare and challenging to diagnose due to nonspecific clinical features. Highlighting such cases can improve early recognition and management. Patient concerns: A 56-year-old man with esophageal cancer developed fatigue, polyuria, polydipsia, dizziness, and severe hyponatremia after treatment with tislelizumab, a PD-1 inhibitor. Diagnoses: Laboratory evaluation revealed new-onset autoimmune diabetes, hypothyroidism, and secondary adrenal insufficiency. The constellation of biochemical abnormalities and clinical features, in the absence of alternative etiologies, indicated immune-related hypophysitis and pancreatic islet injury. Two additional cases of severe, recurrent hyponatremia after PD-1 therapy were also reviewed. Interventions: The patient received targeted hormone replacement therapy, including glucocorticoids and levothyroxine, along with insulin for glycemic control. Outcomes: Symptoms improved significantly, and biochemical parameters normalized following treatment, demonstrating effective management of multi-glandular endocrine failure induced by PD-1 blockade. Lessons: PD-1 inhibitors can cause severe, concurrent dysfunction of multiple endocrine organs. Clinicians should maintain high vigilance, implement proactive screening for pituitary and metabolic abnormalities during and after immune checkpoint inhibitor therapy, and adopt a multidisciplinary approach to ensure timely diagnosis and treatment.

Background: Pyrethroids (PYRs) are increasingly detected in both environmental matrices and human populations. Emerging evidence underscores their potential for systemic toxicity. Biopsy-confirmed nephrotoxicity in humans remains sparsely documented, particularly in non-occupational exposure. We present a case of acute kidney injury (AKI) associated with household pyrethroid-containing aerosol insecticide exposure. Case presentation: A 55-year-old previously healthy male presented with nausea and abdominal pain and was found to have AKI on laboratory evaluation. He denied prior medication use or history of drug allergies. Detailed history revealed that the patient had stayed overnight in a small, poorly ventilated bedroom that had been heavily sprayed with a household pyrethroid-containing aerosol insecticide earlier that evening. Despite receiving empirical treatment, the patient’s renal function progressively deteriorated. Kidney biopsy revealed acute tubular necrosis (ATN) together with acute interstitial nephritis (AIN). After corticosteroid therapy, his renal function partially improved within 3 weeks. During follow-up, renal function stabilized at stage 3 chronic kidney disease (CKD). Conclusion: The case suggests that inappropriate exposure to PYRs may be associated with clinically significant nephrotoxicity, a complication rarely described in humans. Clinicians should consider this environmental toxicant in the differential diagnosis of otherwise unexplained AKI. In addition, the literature review provides mechanistic insights into PYR-associated nephrotoxicity, particularly oxidative stress, inflammation, mitochondrial dysfunction, and tubular injury.

Insecticides have been widely utilized in modern agriculture, as well as in non-agricultural settings such as households and parks for pest control, owing to their low cost and accessibility (Topal...

Purpose: Mast cells (MCs) act as sentinels of the immune system and are involved in peritoneal fibrosis (PF), but the precise mechanism remains unclear. To investigate this, we focused on Astragalus membranaceus and Salvia miltiorrhiza (AS), a combination known for its anti-inflammatory properties. This study aimed to elucidate the effect of AS on MCs and its potential to alleviate PF. Methods: The major chemical components of AS were identified by UPLC-Q-TOF-MS/MS. Subsequently, we employed network pharmacology, molecular docking, and molecular dynamics simulations to investigate the key targets and mechanisms of AS in the treatment of PF. In vivo, a mouse PF model was established by daily intraperitoneal injection of high-glucose (4.25%) peritoneal dialysis fluid (PDF) for 4 weeks. Following AS treatment, the mechanism was explored through transcriptomics analysis, immunohistochemistry (IHC), immunofluorescence (IF), and Western blotting (WB). In vitro, an activated MC model was established by stimulating murine P815 mast cells with LPS. The activation of P815 cells was assessed using transcriptomics analysis, ELISA, and transmission electron microscopy (TEM). Finally, a fibrosis model was further generated by stimulating human peritoneal mesothelial cells (HMrSV5) with tryptase, and the effects of AS were assessed by WB. Results: UPLC-Q-TOF-MS/MS identified 40 active components in AS. Network pharmacology and molecular docking indicated favorable predicted binding affinities of the key constituents calycosin and tanshinone IIA to MAPK1 and NF-κB1, with binding energies ranging from − 9.1 to − 6.8 kcal/mol. In vivo experiments demonstrated that high-glucose PDF increased peritoneal tryptase levels by approximately 3.2-fold, whereas AS treatment reduced tryptase release by 71.5%, respectively (baseline-corrected). Correspondingly, AS significantly inhibited MC degranulation and suppressed activation of the PAR2/MAPK/NF-κB pathway. In vitro, AS decreased LPS-induced tryptase and TNF-α secretion in P815 cells by 71.6% and 58.2%, respectively, and attenuated tryptase-induced fibrosis in HMrSV5 cells, accompanied by reduced phosphorylation of MAPK/NF-κB signaling proteins. Conclusion: This study demonstrates that the MC tryptase/PAR2 signaling axis contributes to PDF-induced peritoneal fibrotic responses. AS alleviates PF at least in part by inhibiting tryptase-mediated MC-PMC crosstalk and downstream PAR2/MAPK/NF-κB activation. Mast cell activation causes peritoneal fibrosis, affected by Astragalus and Salvia.The diagram illustrates the process of mast cell activation leading to peritoneal fibrosis. At the top, Astragalus membranaceus and Salvia miltiorrhiza are shown as influencing factors. Below, an activated mast cell releases substances affecting peritoneal mesothelial cells. The central section depicts tryptase interacting with PAR2, leading to activation of pathways involving p-JNK, p-p38 and p-ERK1/2. This results in NF-kappa B activation, producing TNF-alpha and IL-1 beta, which contribute to peritoneal fibrosis. The sequence shows the progression from mesothelial cell interaction to fibrosis development.