OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

Paradoxical psoriasis is a special adverse drug reaction characterized by the new onset, exacerbation, or phenotypic change of psoriatic lesions during treatment with biological agents. In recent years, with the increasing use of biologics, this condition has garnered growing attention from clinicians. The pathogenesis of paradoxical psoriasis is complex and its clinical manifestations are highly heterogeneous. Diagnosis currently relies primarily on clinical features and medication history due to the lack of unified diagnostic criteria. Furthermore, treatment strategies—such as whether to discontinue the original biologic agent or switch therapies—remain controversial, posing significant challenges in clinical management.This article presents a case of paradoxical psoriasis occurring in a patient with ankylosing spondylitis following treatment with the tumor necrosis factor-α inhibitor (TNFi) infliximab. By discussing the clinical characteristics of this case, we aim to enhance clinicians' understanding of this condition, reduce misdiagnosis and underdiagnosis, and provide valuable insights for its diagnosis and treatment.

Objective:To explore the impact of hypophosphatemia on the occurrence and prognosis of critically ill patient.Methods:The clinical data of critically ill patients admitted to the intensive care unit (ICU) of Tianjin First Central Hospital from October 2021 to April 2022 were retrospectively analyzed. Patients were divided into hypophosphatemia group (serum phosphorus level < 0.80 mmol/L) and non-hypophosphatemia group (serum phosphorus level ≥ 0.80 mmol/L) when they were admitted to the ICU. The following variables were also collected, including gender, age, acute physiology and chronic health evaluationⅡ(APACHE Ⅱ), sequential organ failure assessment (SOFA), serum phosphorus level, serum calcium level, serum magnesium level, white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP), presence of infection and infection site, length of hospital stay, ICU stay, 28-day mortality, and mechanical ventilation time. Multivariate Logistic regression analysis was used to evaluate the relationship between each variable and the 28-day mortality. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) and 95% confidence interval (95% CI) were calculated to evaluate the predictive value of serum phosphorus levels for the prognosis of ICU patients. Results:A total of 263 patients were enrolled, including 54 patients with hypophosphatemia and 209 patients without. The SOFA score, LYM level and the infection rate of patients in the hypophosphatemia group were significantly higher than those in the non-hypophosphatemia group [SOFA score: 6.70±3.17 vs. 5.64±3.59, LYM (×10 9/L): 0.99±0.54 vs. 0.77±0.54, infection rate: 77.78% (42/54) vs. 59.33% (124/209), all P < 0.05], the NLR was significantly lower than that of the non-hypophosphatemia group [10.67 (7.08, 18.02) vs. 12.25 (7.25, 21.68), P < 0.05]. The length of hospital stay, ICU stay, and mechanical ventilation duration in the hypophosphatemia group were significantly longer than those in the non-hypophosphatemia group [length of hospital stay (days): 15 (11, 28) vs. 12 (6, 21), length of ICU stay (days): 10.35±7.80 vs 7.15±6.61, mechanical ventilation duration (days): 3 (0, 12) vs. 2 (0, 5), all P < 0.05]. There was no significant difference in the 28-day mortality between the hypophosphatemia group and the non-hypophosphatemia group [9.26% (5/54) vs. 11.00% (23/209), P > 0.05]. Multivariate Logistic regression analysis showed that APACHE Ⅱ score [odds ratio ( OR) = 1.188, 95% CI was 1.110-1.271], CRP ( OR = 1.016, 95% CI was 1.007-1.026), and NLR ( OR = 1.002, 95% CI was 0.996-1.008) were independent risk factors affecting the 28-day mortality of critically ill patients in ICU (all P < 0.05). ROC curve analysis showed that the AUC of serum phosphorus levels for predicting the length of hospital stay of critically ill patients in ICU > 10 days, ICU stay > 5 days, and mechanical ventilation duration > 5 days were 0.701 (95% CI was 0.632-0.770), 0.771 (95% CI was 0.691-0.852), 0.617 (95% CI was 0.541-0.692), respectively, all P < 0.01. Conclusion:Hypophosphatemia has some predictive value for the length of hospital and ICU stay and mechanical ventilation time in critically ill patients, but it cannot predict the 28-day mortality.

To investigate the security of semen biologically, 15 bull semen samples were collected (of which 5 exhibited clinical signs of Foot-and-mouth disease) and identified by RT-PCR and virus isolation. The results indicated that the semen of the infected bulls were contaminated by Foot-and-mouth disease virus (FMDV), but FMDV was not detected in semen samples from those bulls not showing clinical signs of Foot-and-mouth disease (FMD). This is the first report of the presence of FMDV in bull semen due to natural infection in China. The analysis of the partial sequence of the VP1 gene showed that the virus strain isolated from semen has 97.9% identity with the virus isolated from vesicular liquid of infected bulls showing typical signs of FMD and belonged to the same gene sub-group.