Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Iron is an essential trace element in the human body, crucial in maintaining normal physiological functions. Recent studies have identified iron ions as a significant factor in initiating the ferroptosis process, a novel mode of programmed cell death characterized by iron overload and lipid peroxide accumulation. The iron metabolism pathway is one of the primary mechanisms regulating ferroptosis, as it maintains iron homeostasis within the cell. Numerous studies have demonstrated that abnormalities in iron metabolism can trigger the Fenton reaction, exacerbating oxidative stress, and leading to cell membrane rupture, cellular dysfunction, and damage to tissue structures. Therefore, regulation of iron metabolism represents a key strategy for ameliorating ferroptosis and offers new insights for treating diseases associated with iron metabolism imbalances. This review first summarizes the mechanisms that regulate iron metabolic pathways in ferroptosis and discusses the connections between the pathogenesis of various diseases and iron metabolism. Next, we introduce natural and synthetic small molecule compounds, hormones, proteins, and new nanomaterials that can affect iron metabolism. Finally, we provide an overview of the challenges faced by iron regulators in clinical translation and a summary and outlook on iron metabolism in ferroptosis, aiming to pave the way for future exploration and optimization of iron metabolism regulation strategies.

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Objective: To evaluate the impact of the targeted next-generation sequencing (NGS) assay for difficult congenital anemias. Methods: Blood Disease Hospital Anemia Panel 2014 (BDHAP-2014) including 217 known genes of congenital anemias was developed. NGS and parental verification were performed for patients who were suspected diagnosed with congenital anaemia from August 2014 to July 2017. Results: A total of 46 patients were enrolled in this study, the clinical suspection were 11 cases Fanconi anemia (FA), 8 cases congenital dyserythropoietic anemia (CDA), 6 cases congenital sideroblast anemia (CSA), 12 cases congenital hemolytic anemia (CHA), 1 case dyskeratosis congenital (DC), 4 cases iron-refractory iron deficiency anemia and 4 cases unexplained cytopenia (Uc), respectively. 28 (60.9%) of 46 patients became confirmed cases after targeted NGS, corresponding to 44 mutations of which 33 were new. 26(56.5%) patients with results of the assay matching to clinical suspection, including FA (5/11, 45.5%), CSA (6/6, 100.0%), CDA (3/8, 37.5%) and CHA (12/12, 100.0%). 2 (4.3%) cases not matching to clinical suspection, including dyskeratosis congenital (DC) was made in 1(2.2%) patients with suspected FA and familial hemophagocytic lymphohistiocytosis (FHL) was made in 1(2.2%) patients with suspected unexplained cytopenia (Uc). In 12 CHA patients, the hemolytic type was further clarified by the NGS. The remaining 18 cases were not clearly diagnosed. Conclusion Targeted NGS assay is of major impact on congenital anemias. The assay should be used routinely in congenital anemias.

Objective To investigate the influence of preoperative anxiety-depression status on the postoperative pain in patients undergoing gynecologic laparoscope surgery.Methods Ninety pa-tients,aged 18-65 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ,undergoing gynecologic laparoscope surgery were included in this single-center observational study.All the patients were in-terviewed by anesthetists the afternoon before surgery and completed a Hospital Anxiety and Depres-sion Scale (HADS)to evaluate the anxiety-depression status.Then the patients were divided into two groups,low HADS group (group L)(HADS score≤9)and high HADS group (group H)(HADS score>9).Patients'visual analogue scores (VAS)were recorded at the time 30 min,60 min,6 h, 12 h,24 h after operation.The correlation analysis between HADS before operation and VAS scores at different time point was performed.The use of analgesia medicine,exhausting time and complica-tions such as nausea, vomiting, dizzy, pain of shoulder and back were also recorded. Results Compared to group H,VAS score was lower in group L at 6 hour after surgery but no sig-nificant different was found at 30 min,60 min,12 h,24 h after surgery.There was a significant asso-ciation between preoperative HADS scores and VAS at 6 hour after surgery (r=0.634,P=0.01);but no significant association was found between preoperative HADS scores and VAS at the other time point after surgery.The exhausting time was significantly longer in group H than group L (P<0.05).There was no significant difference in the incidence of nausea,vomiting,dizzy or pain of shoulder and back between the two groups.Conclusion Preoperative anxiety-depression status has a positive influence on postoperative pain at 6 hour after gynecologic laparoscope surgery,and also can delay the recovery of gastrointestinal function.

The paper analyzes proposing and development of the concept of information literacy of clinical nurses and its relations with evidence-based nursing, nursing scientific research and clinical nursing, summarizes current situation and main opinions on influ-encing factors of the study, summarizes the methods and strategies to enhance information literacy of the clinical nurses, and tells the main direction and key points of the study on information literacy of clinical nurses.

Objective To study the relationship between the level of serum epithelial fatty acid binding protein (E-FABP) and cardiovascular disease in obese children. Methods Thirty children with metabolic syndrome (MS), 32 obesity children with no MS and 50 healthy children were recruited. Serum E-FABP and glucose/lipid metabolic indices were measured. Results Com-pared with the healthy children, levels of serum E-FABP in MS children were signiifcantly elevated (P=0.001). Compared with obesity children, levels of serum E-FABP of MS children were elevated, but the difference was not signiifcant (P>0.05). The cor-relations of E-FABP with waist to hip ratio, waist-to-height ratio, atherogenic index, fasting insulin, insulin resistance index were positive (P<0.05). According to the multivariate stepwise regression analysis, E-FABP was the independent risk of atherogenic index (P=0.018). Conclusions E-FABP plays a role in the development of atherosclerosis in obesity and MS.

Objective To investigate the predictive value of plasma cystatin C (CysC) in patients with acute coronary syndrome (ACS) after pereutaneous coronary intervention (PCI).Methods A total of 660 patients with ACS admitted to cardiovascular department were enrolled in this study from January 2009 to June 2010.The enrollment criteria were:(1) the stenosis degree was above 75％ in at least one coronary artery checked by coronary angiography and successful PCI; (2) normal renal function or mild dysfunction with glomerular filtration rate (GFR) ＞ 60 ml/ ( min · 1.73 m2 ).Exclusion criteria were severe liver and renal insufficiency,malignancies and valvular heart diseases.The plasma CysC levels were examined by the latex enhanced immune turbidity method within 24 hours after admission.The relevant clinical data were recorded.The patients were followed up by out-patient interview or telephone from March to June 2011 and adverse cardiovascular events were recorded.The patients were divided into four groups according to CysC level:Q1 (CysC＜1.02 mg/L),Q2 (1.02 mg/L≤＜CysC ＜1.17 mg/ L),Q3 (1.17 mg/L ≤ CysC ＜1.35 mg/L) and Q4 (CysC ≥ 1.35 mg/L).Univariate and multivariate Cox hazards regressions were established to analyze the factors related to prognosis.The proportion differences between four groups were tested by x2.The survival ratio was estimated using the Kaplan-Meier method.Statistical significance was established at a P value of less than 0.05.Results ① A total of 606 ( 91.7％ ) patients successfully accepted follow-up.Mean follow-up time was ( 14.3 + 1.7 ) months.Of them,95 patients were subjected to adverse cardiovascular events ( 15.7％ ).②The incidences of adverse cardiovascular events in Q2,Q3,Q4 were significantly higher than those in Q1 ( P ＜ 0.001 ).The rates of mortality,nonfatal myocardial infarction and target lesion revascularization in Q4 were higher than those in Q1 ( P ＜ 0.05 ).The incidences of heart failure in Q3 and Q4 were higher than that in Q1 ( P ＜ 0.05 ).③Univariate analysis demonstrated that CysC,creatinine,LVEF,age,history of PCI and NYHA grade ≥3 were the risk factors of poor prognosis (P ＜ 0.05 ).④ Multivarite cox hazards regression revealed that the elevation of CysC level remained an independent predictor of adverse cardiovascular events.The relative risk of Q3 and Q4 were 3.930 (95％ CI 1.306-11.829,P =0.015 ) and 6.380 (95％ CI 2.171-18.751,P =0.001 ) compared with Q1.⑤　The cumulative rates of survival without adverse cardiovascular events in Q2,Q3 and Q4 decreased compared with Q1 (P ＜ 0.001 ).Conclusions High plasma CysC concentration is an independent predictor of adverse cardiovascular events in patients with ACS after PCI.

In order to realize the sustained education concept in clinical medical English teaching,several measures were taken in the first clinical medical college of Nanjing University of Traditional Chinese Medicine,such as training the teaching staff,using original textbooks and redesigning the curriculum.Particularly the tutorial system was introduced to the education frame.The teaching and research section of clinical medical English explored the new teaching routes for postgraduates in traditional Chinese medicine university.