Objective To establish a prediction model for the occurrence of non-occupational carbon monoxide poisoning events in Beijing, and to provide scientific basis and theoretical support for the prevention and warning of poisoning events. Methods Based on the monitoring data of non-occupational carbon monoxide poisoning events in Beijing from 2016 to 2024, the seasonal ARIMA model and seasonal index model were established to analyze the data and predict the occurrence of events. Results Between 2016 and 2024, a total of 436 cases of non-occupational carbon monoxide poisoning were reported in Beijing, showing a downward trend. The established SARIMA model and seasonal index model were SARIMA (1,0,0) (1,1,0) 12, Yt = (-0.0339t+5.8863) × St, and the average relative errors were 65.42% and 29.19%, respectively. In terms of months, the SARIMA model had better predictive performance during April and summer (June to August), while the seasonal index model was superior in other months. By combining the two models, the predicted number of events in 2025 was as follows: 3, 2, 2, 3, 1, 5, 2, 7, 1, 1, 1, and 2. Conclusion The seasonal index model has the best prediction effect on the non-occupational carbon monoxide poisoning events in Beijing throughout the year, and the number of summer events predicted by SARIMA model is closer to the actual values. The two models can be combined to predict the trend of non-occupational carbon monoxide poisoning, which provides a scientific basis for the prevention and control of carbon monoxide poisoning in the future.

OBJECTIVE: To observe the protective effect of Fisetin on sepsis-associated brain injury and explore its possible mechanism from the perspective of ferroptosis. METHODS: Sprague-Dawley (SD) rats (6-8-week-old male) were randomly divided into three groups: sham operation group (Sham group), colonic ligation and puncture (CLP) induced sepsis model group (CLP group) and Fisetin preprocessing group (CLP+Fisetin group), with 18 rats in each group (12 for observing survival rate and 6 for indicator testing). The CLP+Fisetin group was given Fisetin solution 50 mg×kg^-1×d^-1 by gavage continuously for 5 days before CLP, with dimethyl sulfoxide (DMSO) as the solute, while Sham group and CLP group were given the same dose of DMSO. The model was established at 2 hours after the last gavage. The general condition of each group of rats were observed, and the 10-day mortality were record. The behavioral testing (new object recognition experiment, elevated cross maze experiment) were performed after 7 days of modeling. After 24 hours of modeling, nerve reflex scoring was performed, and then the rats were euthanized and brain tissue was collected. The pathological changes of brain tissue were observed under a microscope by hematoxylin-eosin (HE) staining, the deposition of iron ion in brain tissue was observed by Prussian blue staining. The content of iron in brain tissue was determined by tissue iron kit, and the content of malondialdehyde (MDA) in brain tissue was determined by colorimetry. The expressions of tumor necrosis factor-α (TNF-α), neuron damage marker S100β, nuclear factor E2-related factor 2 (Nrf2), heme oxygenases-1 (HO-1) and glutathione peroxidase 4 (GPX4) were detected by Western blotting. RESULTS: On day 10 post-operation, 12, 3, and 7 animals survived in the Sham group, CLP group, and CLP+Fisetin group, respectively. Compared with the Sham group, rats in the CLP group showed significantly decreased nerve reflex score, new object discrimination index and open arm dwell time. HE staining showed arranged disorderly of neuronal cells, cytoplasm deep staining, nuclear condensation, unclear structures, neuron loss, and significant inflammation in the hippocampus in the hippocampus. Prussian blue staining showed iron ion deposition in the brain tissue. The contents of iron and MDA in brain tissue were elevated, and the expressions of TNF-α and S100β were up-regulated, while the expressions of Nrf2, HO-1, and GPX4 were down-regulated. Compared with the CLP group, the CLP+Fisetin group showed significantly increased neurological reflex score (7.33±1.15 vs. 4.67±1.53), improved new object discrimination index (0.44±0.02 vs. 0.32±0.04), and longer open arm dwell time (minutes: 78.33±9.29 vs. 41.15±9.64). Neuronal cells in the hippocampus were more organized, with less cytoplasmic staining, nuclear condensation, reduced neuronal loss, and fewer inflammatory cells. Iron ion deposition was reduced, and the contents of iron ions and MDA in brain tissue were decreased [iron ion (μg/g): 151.27±14.90 vs. 224.69±17.64, MDA (μmol/g): 470.0±44.3 vs. 709.3±65.4]. The expressions of TNF-α and S100β were significantly decreased (TNF-α/GAPDH: 0.651±0.060 vs. 0.896±0.022, S100β/GAPDH: 0.685±0.032 vs. 0.902±0.014), while the expressions of Nrf2, HO-1, and GPX4 were significantly increased (Nrf2/GAPDH: 0.708±0.108 vs. 0.316±0.112, HO-1/GAPDH: 0.694±0.022 vs. 0.538±0.024, GPX4/GAPDH: 0.620±0.170 vs. 0.317±0.039). All differences were statistically significant (all P < 0.05). CONCLUSION Fisetin pretreatment can inhibit ferroptosis and reduce sepsis-associated brain injury by Nrf2/HO-1/GPX4 pathway.
Animals ; Ferroptosis/drug effects* ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/metabolism* ; Sepsis/complications* ; Male ; Rats ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Neurons/drug effects* ; Signal Transduction ; Brain Injuries/metabolism* ; Flavonols ; Flavonoids/pharmacology* ; Heme Oxygenase-1/metabolism* ; Heme Oxygenase (Decyclizing)

Immunotherapy following transplantation has long been a central focus in both anti-rejection strategies and the induction of immune tolerance. Regulatory B cells (Bregs) can directly suppress the immune system via the interaction between programmed cell death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1). Additionally, Bregs exert indirect immunosuppressive effects through the secretion of cytokines such as interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and granzyme B (GrB), among which IL-10 plays a particularly critical role. This review summarizes recent progress in the classification, functional characteristics, and activation mechanisms of Bregs, as well as their potential applications in transplantation immunotherapy, aiming to provide a theoretical foundation for Breg-targeted strategies in transplant immune modulation.

Acute kidney injury(AKI)is a syn-drome characterized by rapid decline in renal excre-tory function.Its pathogenesis is still unclear.Stud-ies have shown that macrophages are major play-ers in AKI inflammation,regulating tissue damage and regeneration repair.During AKI inflammation,macrophages can be activated into different func-tional phenotypes through molecular and signaling pathways,regulate different molecules and signal-ing pathways,and determine the progression of AKI.In this paper,the activation of macrophages and the molecular signaling pathways involved in the regulation of AKI in the past five years are re-viewed,and the mechanism of action of macro-phages in AKI is determined,which provides ideas for the study of macrophages as therapeutic tar-gets.

Acute kidney injury(AKI)is a syn-drome characterized by rapid decline in renal excre-tory function.Its pathogenesis is still unclear.Stud-ies have shown that macrophages are major play-ers in AKI inflammation,regulating tissue damage and regeneration repair.During AKI inflammation,macrophages can be activated into different func-tional phenotypes through molecular and signaling pathways,regulate different molecules and signal-ing pathways,and determine the progression of AKI.In this paper,the activation of macrophages and the molecular signaling pathways involved in the regulation of AKI in the past five years are re-viewed,and the mechanism of action of macro-phages in AKI is determined,which provides ideas for the study of macrophages as therapeutic tar-gets.

Immunotherapy following transplantation has long been a central focus in both anti-rejection strategies and the induction of immune tolerance. Regulatory B cells (Bregs) can directly suppress the immune system via the interaction between programmed cell death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1). Additionally, Bregs exert indirect immunosuppressive effects through the secretion of cytokines such as interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and granzyme B (GrB), among which IL-10 plays a particularly critical role. This review summarizes recent progress in the classification, functional characteristics, and activation mechanisms of Bregs, as well as their potential applications in transplantation immunotherapy, aiming to provide a theoretical foundation for Breg-targeted strategies in transplant immune modulation.

Renal fibrosis, especially tubulointerstitial fibrosis, is the most common pathway of all chronic kidney diseases progressing to end-stage renal diseases. Several adaptive reactions occur in renal tubular epithelial cells after chronic injury, such as changes in glycolipid metabolism, unfolded protein response, autophagy and senescence, epithelial-to-mesenchymal transition and G2/M cell cycle arrest. Maladaptive repair mechanisms can induce tubulointerstitial fibrosis. This article will discuss the molecular mechanism of these adaptive responses of renal tubular epithelial cells driving renal tubulointerstitial fibrosis, and provide a basis for exploring new drug targets for renal tubulointerstitial fibrosis.

OBJECTIVE To study the pharmacokinetics and pharmacodynamics of oral colon targeted pH-sensitive hydrogel of hydrocortisone sodium succinate(HSS-GEL). METHODS The plasma concentration changes of HSS-GEL and HSS in the mice were investigated; 2, 4, 6-trinitrobenzene sulfonic acid(TNBS)-induced mouse model of ulcerative colitis(UC) was established, disease activity index(DAI), colon length, myeloperoxidase(MPO) and organ index were used as indicators to investigate the therapeutic effect of HSS-GEL on colitis. RESULTS The results showed that the Tmax, Cmax and AUC of HSS-GEL were significantly different from those of HSS(P<0.01). The Tmax of HSS-GEL was significantly longer than that of HSS, and the time of drug absorption into the blood was significantly delayed. The Cmax of HSS-GEL group was significantly lower than that of HSS. The AUC of the HSS-GEL group was 39.38% of the same dose of HSS, indicating that the amount of the drug absorbed into blood was significantly reduced after the HSS was made into HSS-GEL orally. After modeling, DAI, MPO activity and organ index were increased, while the colon was shortened due to the inflammatory reaction, with the treatment of HSS-GEL, DAI, MPO activity and some organ index of mice were significantly decreased comparing with TNBS group(P<0.05 or P<0.01). The degree of reduction of MPO activity and some organ indexes of the mice in the TNBS+HSS-GEL group were significantly greater than those in the TNBS+HSS group, indicating that HSS-GEL had good therapeutic effect on TNBS-induced ulcerative colitis, and the effect was better than that of HSS. CONCLUSION The HSS-GEL prepared has good colon targeting characteristic and colitis treatment effect.

Objective To study the absorption features of isoimperatorin in intestine of rat.Methods Establish a single-pass intestinal perfusion model of rat,take phenolsulfonphthalein as a marker for the detection of isoimperatorin concentration from crude extracts of notopterygium,and observe the absorption features of isoimperatorin and its reference substance in intestine of rat.Results The content of isoimperatorin in crude extracts was (0.43±0.02)% (n=5).The absorption parameters of duodenum,jejunum,ileum,colon were (5.28±0.82),(4.47±0.56),(4.17±0.94),(4.32±0.68)×10-5 cm·s-1,respectively.There were no significant differences among them (P>0.05).Compared with the reference substance of isoimperatorin,crude extracts showed better absorption features.Conclusion Isoimperatorin from crude extracts have better characteristics of absorption.This study can provide theoretical basis for design of notopterygium oral formulation.

Objective: To explore the clinical significance of metastasis of lymph nodes between sternocleidomastoid and sternohyoid muscle (LNSS) in papillary thyroid cancer (PTC). Methods: A total of 175 patients with PTC who underwent thyroidectomy with LNSS dissection were retrospectively analyzed. Univariate and multivariate Logistic regression analyses were used to determine the independent risk factors for LNSS metastasis in PTC. Results: The rate of detectable LNSS was 70.9% (124/175) and metastasis rate was 7.4% (13/175). Of 13 cases with LNSS metastasis, 10 with the coexistence of cervical lymph node metastasis. Univariate Logistic regression analysis showed that multiple focal cancer, tumor located in the lower pole of thyroid, belt-shaped muscle invasion, lateral cervical lymph node metastasis, cN+ , the number of cervical lymph nodes with metastasis and the number of lymph nodes with metastasis in level Ⅳwere the risk factors for LNSS metastasis (P<0.05). Multivariate Logistic regression analysis suggested that tumor located in the lower pole of thyroid and the number of cervical lymph nodes with metastasis >6 were the independent risk factors for LNSS metastasis (P<0.05). Given the number of cervical lymph nodes with metastasis as a predictor for the LNSS metastasis, the sensitivity was 92.3%, the specificity was 66.7% and the accuracy rate was 68.6%. Conclusions LNSS metastasis is commom in PTC, with a metastasis rate of 7.4%. PTC in the lower pole of thyroid and the number of cervical lymph nodes with metastasis > 6 are independent risks for LNSS metastasis.