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.

Immunotherapy has become a pivotal modality in clinical cancer treatment. However, its effectiveness is limited to a small subset of patients due to the low antigenicity, impaired innate response, and various adaptive immune resistance mechanisms of the tumor microenvironment (TME). Accumulating evidence reveals the critical roles of metal elements in shaping immunity against tumor progression and metastasis. The marriage of metalloimmunotherapy and nanotechnology further presents new opportunities to optimize the physicochemical and pharmacokinetic properties of metal ions in a precise spatiotemporal control manner. Several metallodrugs have demonstrated encouraging immunotherapeutic potential in preliminary studies and are currently undergoing clinical trials at different stages, yet challenges persist in scaling up production and addressing long-term biosafety concerns. This review delineates how metal materials modulate biological activities across diverse cell types to orchestrate antitumor immunity. Moreover, it summarizes recent progress in smart drug delivery-release systems integrating metal elements, either as cargo or vehicles, to enhance antitumor immune responses. Finally, the review introduces current clinical applications of nanomedicines in metalloimmunotherapy and discusses potential challenges that impede its widespread translation into clinical practice.

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 understand the gene carrying rate of neonatal genetic deafness in Dalian area, and to analyze the pedigree of 6 newborns with positive deafness gene test, to provide a reference basis for preventing genetic deafness.Methods:A total of 1 536 newborns born in Dalian Women′s and Children′s Medical Center (Group) from January to October in 2022 were retrospectively enrolled to detect the 4 genes of hereditary deafness, including GJB2, GJB3, SLC26A4 (PDS) and MT-RNRI (12SrRNA). Among them, 6 newborns with hereditary deafness were tested for NGS Panel gene.Results:A total of 85 deafness gene mutations were detected in 1 536 newborns, with the total carrying rate of 5.53% (85/1 536). Thirty-two cases of GJB2 mutations with carrying rate of 2.08% (32/1 536); 4 cases of GJB3 mutation of 0.26% (4/1 536); 32 cases of SLC26A4 (PDS) gene mutations of 2.08% (32/1 536); 14 cases of MT-RNRI (12SrRNA) mutations with carrying rate of 0.91% (14/1 536); 2 cases had compound heterozygous mutations of GJB2/GJB3, with a carrier rate of 0.13% (2/1 536); 1 cases had compound heterozygous mutations of GJB2/SLC26A4 (PDS), with a carrier rate of 0.07% (1/1 536); 1 case of compound heterozygous mutation in three-gene and a heterozygous mutation in KCNQ4 were detected in NGS Panel testing for hereditary deafness.Conclusions:Homozygous mutation and compound heterozygous mutation are the main factors of autosomal recessive gene deafness, and the NGS Panel gene detection is of great significance for gene traceability and the detection of rare deafness gene.

Objective To investigate the incidence and severity of symptoms in patients with gastric cancer who received chemotherapy,we constructed a symptom network to explore core symptoms and bridge symptoms.Furthermore,the study explores the association between core symptoms and Traditional Chinese Medicine(TCM)constitutions.Methods Patients with gastric cancer who received chemotherapy in the medical oncology and surgical oncology department from March to August 2023 were selected for the study using a convenience sampling method.The MD Anderson Symptom Inventory Gastrointestinal Cancer was used for evaluating gastrointestinal symptoms and their severity among patients receiving chemotherapy for gastric cancer,as well as assessing the classification of TCM constitution among patients.The symptom network model was constructed using the R programming language,and the central index was analyzed to determine the core symptoms and bridge symptoms.Binary logistic regression analysis was employed to assess the association between different physical conditions and the occurrence of core symptoms.Results A total of 346 electronic questionnaires were collected,with 340 valid ones,and the effective recovery rate was 98.3％.The 3 most prevalent and severe symptoms among the 340 patients with gastric cancer were fatigue(85.59％),lack of appetite(82.35％),and taste alteration(81.18％).The centrality index results indicated that grief exhibited the highest intensity,medium,and compactness centrality values(rs=8.23,rb=2.00,rc=0.03),making it the core symptom of this condition.Sleep disorders,lack of appetite,drowsiness,and taste alteration were identified as bridging symptoms with bridge intensities of 0.74,0.76,0.99,and 0.94 respectively.The results of Spearman correlation analysis showed that there was a positive correlation between sadness and qi-deficiency constitution,phlegm-dampness constitution(P＜0.05).The phlegm-dampness constitution was positively correlated with the taste alterations(P＜0.05).Conclusion In patients with gastric cancer,fatigue emerges as the most prominent symptom,while sadness assumes the core symptom.Additionally,sleep disorder,lack of appetite,drowsiness,and taste alteration are bridge symptoms.According to the principles of TCM constitution,qi-deficiency and phlegm-dampness are constitutions associated with a higher risk of experiencing sadness,and phlegm-dampness is a constitution associated with a higher risk of taste changes.Nurses can integrate core symptoms and TCM constitutions characteristics to optimize the strategies for symptom intervention.

Objective:To investigate the factors influencing the decision to delivery interval (DDI) in emergency cesarean section in Guangzhou and the impact of DDI on maternal-infant outcomes.Methods:A retrospective study was conducted on clinical data of pregnant women who underwent emergency cesarean section at municipal and district maternal and child health hospitals in Guangzhou city in 2021. Per the classification method of emergency cesarean section and recommendations for DDI provided by National Institute for Health and Clinical Excellence guidelines, these subjects were classified into Category Ⅰ and Category Ⅱ cesarean sections. Each category was further divided into two subgroups based on DDI: the Category Ⅰ group into >30 min and ≤30 min subgroups, and the Category Ⅱ group into >75 min and ≤75 min subgroups. Chi-square test or Fisher's exact test, two independent samples t-test, Mann-Whitney U test, and logistic regression were used to analyze the potential factors influencing DDI and the impact of DDI on maternal-infant outcomes. Results:(1) Totally 502 women underwent urgent cesarean section, including 304 (60.6%) Category Ⅰ and 198 (39.4%) Category Ⅱ, were analyzed. Among the Category Ⅰ group, 30.3% (92/304) achieved a DDI of ≤30 min, while 37.4% (74/198) of Category Ⅱ cases had a DDI of ≤75 min. (2) For the Category Ⅰ cases, multivariate logistic regression showed that more patients under intravertebral anesthesia, than those under general anesthesia, had a DDI >30 min ( OR=14.04, 95% CI: 6.14-32.10) as well as more with ward-based emergencies than those with delivery room emergencies ( OR=3.21, 95% CI: 1.72-6.00, both P=0.001). Among the Category Ⅱ cases, logistic regression revealed that cesarean section during routine working hours was more likely to achieve DDI >75 min than that during resting hours ( OR=3.93, 95% CI: 2.03-7.63, P=0.001). The risk of DDI >75 min was higher in tertiary maternal and child health hospitals compared with secondary maternal and child health hospitals ( OR=2.45, 95% CI: 1.06-5.70, P=0.037). (3) Among the Category Ⅰ cases, compared with the DDI ≤30 min group, the DDI >30 min group had a lower risk of neonatal Apgar score ≤7 at 1 min ( OR=0.31, 95% CI: 0.14-0.69, P=0.004), but there was no significant difference in the risk of neonatal Apgar score ≤7 at 5 min ( OR=0.21, 95% CI: 0.04-1.17) or neonatal asphyxia ( OR=0.32, 95% CI: 0.07-1.44) between the two subgroups. In cases of Category Ⅱ cesarean sections, there was no significant difference in any maternal-infant outcomes between DDI ≤75 min and DDI >75 min subgroups. Conclusions:The location of emergency and types of anesthesia are the influencing factors of DDI for Category Ⅰ cesarean sections, while the operation time and level of maternal and child health hospital are the influencing factors of DDI for Category Ⅱ cesarean sections. We did not find any impact of DDI on maternal or infant outcome.

The research about physiological changes caused by special mechanical environment in aerospace activities have always been important parts of mechanobiology researches.This review summarizes the progress of aerospace mechanobiology researches in 2023,primarily focusing on the biological effects of weightlessness,including results obtained at the cellular,model animal,and human levels under both real space and ground-based simulated weightlessness,so as to assist the development of aerospace mechanobiology,as well as health protection or countermeasures for astronauts and relevant populations on the ground.

Objective:To detect the expression of Toll-like receptor 7(TLR7)in blood neutrophils of patients with allergic rhi-nitis(AR),allergic asthma(AA)and allergic rhinitis combined with allergic asthma(ARA)before and after allergen challenge.Methods:A total of 44 AR,36 AA,19 ARA patients and 19 healthy control(HC)were recruited,the extracts of Artemisia siever-siana wild allergen(ASWE),house dust mite allergen(HDME)and Platanus pollen allergen(PPAE)were used to challenge periph-eral blood of HC as well as the patients,the expression of TLR7 in neutrophils was detected by flow cytometry.Results:In a resting state,compared with HC,upregulated expression of TLR7 in neutrophils in patients with airway allergy:the percentage of TLR7+neu-trophils in AR,AA,ARA patients increased 6 times,3.18 times and 6.15 times,respectively,and the mean fluorescence intensity(MFI)of TLR7 expression in neutrophil in ARA was enhanced by 24%.The results of allergen challenge tests showed that the expres-sion of neutrophils TLR7 did not change in HC subjects after the allergen challenge,whereas the expression of TLR7 in neutrophils of patients with airway allergy was upregulated after the allergens challenge.After HDME and PPAE challenge,the percentage of TLR7+neutrophils in peripheral of AR patients increased by 8.40%and 33.03%,respectively,and the MFI of TLR7 enhanced by 29.62%and 35.72%,respectively.After ASWE and PPAE challenge.The percentage of TLR7+neutrophils in peripheral of AA pa-tients increased by 59.18%and 1.06 times,respectively,and the MFI of TLR7 enhanced by 68.93%and 47.33%,respectively.How-ever,after HDME stimulation only enhanced the MFI of neutrophil TLR7 in AA patients by 66.14%;after HDME challenge,the per-centage of TLR7 and MFI in peripheral blood neutrophils of patients with ARA increased by 21.05%and 35.61%,respectively,while after PPAE challenge,the percentage of TLR7+cells in patients with ARA increased by 20.07%.Conclusion:The expression of TLR7 in blood neutrophils is increased in patients with allergic airway diseases after allergen stimulation,suggesting that allergens may be involved in the occurrence and development of allergic airway diseases by inducing TLR7 expression changes in neutrophils.

Objective:To establish a menstrual prediction model after the first course of hormone replacement therapy(HRT)in premature ovarian insufficiency(POI)patients after allogeneic hematopoietic stem cell transplan-tation(allo-HSCT),and to provide certain reference value for formulating HRT plans.Methods:The retrospective analysis recruited 154 POI patients after allo-HSCT in the First Affiliated Hospital of Soochow University from Jan-uary 2017 to October 2022.They were divided into ideal menstruation group(n=116)and unideal menstruation group(n=38)according to menstruation after the first course of HRT.Basic characteristics and clinical data were compared in single-factor analysis to select predictive factors.Patients were randomly divided into training set and test set.The menstrual prediction model was developed based on random forest algorithm on the training set and the prediction efficiency was verified by the test set.Finally,we made a user interaction interface and deployed to the server for sharing.Results:The single-factor analysis suggested statistic difference of age of visit,body mass index(BMI),gravidity,parity,hematologic diseases,transplantation age,donor gender,follicle-stimulating hormone(FSH),Luteinizing Hormone(LH),lumbar bone mineral density(BMD)and HRT plan(P<0.05).According to mean decrease accuracy,the predictive factors included visit age,transplantation age,BMI,FSH,HRT plans,gravidity and parity.After the initial establishment of the random forest model,we improved it by adjusting ntree to 500,mtry to 6 and training/test set division to 80%/20% .We also used tenfold cross validation to reduce over-fitting.The area under curve(AUC)of the final constructed menstrual prediction model was 0.768,a sensitiv-ity of 0.695 and a specificity of 0.735.Conclusions:This study successfully established a menstrual prediction model for amenorrhea patients after allo-HSCT when finished the first course of HRT.The false positive rate was low,suggesting that if the prediction result of the model is non-ideal menstruation,we may consider adjusting HRT plans to promote menstruation in time.

Objective:To establish a menstrual prediction model after the first course of hormone replacement therapy(HRT)in premature ovarian insufficiency(POI)patients after allogeneic hematopoietic stem cell transplan-tation(allo-HSCT),and to provide certain reference value for formulating HRT plans.Methods:The retrospective analysis recruited 154 POI patients after allo-HSCT in the First Affiliated Hospital of Soochow University from Jan-uary 2017 to October 2022.They were divided into ideal menstruation group(n=116)and unideal menstruation group(n=38)according to menstruation after the first course of HRT.Basic characteristics and clinical data were compared in single-factor analysis to select predictive factors.Patients were randomly divided into training set and test set.The menstrual prediction model was developed based on random forest algorithm on the training set and the prediction efficiency was verified by the test set.Finally,we made a user interaction interface and deployed to the server for sharing.Results:The single-factor analysis suggested statistic difference of age of visit,body mass index(BMI),gravidity,parity,hematologic diseases,transplantation age,donor gender,follicle-stimulating hormone(FSH),Luteinizing Hormone(LH),lumbar bone mineral density(BMD)and HRT plan(P<0.05).According to mean decrease accuracy,the predictive factors included visit age,transplantation age,BMI,FSH,HRT plans,gravidity and parity.After the initial establishment of the random forest model,we improved it by adjusting ntree to 500,mtry to 6 and training/test set division to 80%/20% .We also used tenfold cross validation to reduce over-fitting.The area under curve(AUC)of the final constructed menstrual prediction model was 0.768,a sensitiv-ity of 0.695 and a specificity of 0.735.Conclusions:This study successfully established a menstrual prediction model for amenorrhea patients after allo-HSCT when finished the first course of HRT.The false positive rate was low,suggesting that if the prediction result of the model is non-ideal menstruation,we may consider adjusting HRT plans to promote menstruation in time.