Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Objective:To explore the effect path of death attitude and purpose in life on attitude toward hospice care of undergraduate intern nursing students.Methods:This study was a cross-sectional study. Using the convenient sampling method, a total of 229 undergraduate intern nursing students from two schools in Hefei, Anhui Province were selected as the research objects from October to December 2022. General data questionnaire, Chinese Version of Frommelt Attitudes Toward Care of the Dying Scale Form B (FATCOD-B-C), Chinese Version of Death Attitude Profile-Revised (DAP-R) Scale and Chinese Version of Purpose in Life Test (PIL-C) were used to investigate. Pearson correlation analysis was used to explore the correlation between death attitudes, purpose in life and attitude toward hospice care among undergraduate intern nursing students. Structural equation model was used to examine the path relationship between attitude towards death and purpose in life on attitude toward hospice care.Results:A total of 229 questionnaires were sent out in this study, and 214 were effectively recovered, with an effective recovery rate of 93.45% (214/229). Among 214 undergraduate intern nursing students, the scores of FATCOD-B-C, Chinese Version DAP-R Scale, and PIL-C were (101.06±8.16), (91.21±12.13) and (94.45±11.90), respectively. The results of Pearson correlation analysis showed that the purpose in life was positively correlated with attitude toward hospice care ( r=0.290, P<0.01), while the attitude to death was negatively correlated with attitude toward hospice care ( r=-0244, P<0.01). The results of structural equation model path analysis showed that the purpose in life (life goal, life attitude) can affect attitude toward hospice care through death attitude (escape acceptance, natural acceptance, fear of death) . Conclusions:Effective interventions on purpose in life and attitude towards death of undergraduate intern nursing students can improve their attitudes toward hospice care .

Objective:To explore the relationship between ultrasound characteristics and invasiveness in the follicular variant of papillary thyroid carcinoma (FVPTC), and to integrate multiple ultrasound parameters for visual assessment of predictive outcomes by using Nomogram.Methods:A total of 312 FVPTC patients who were pathologically confirmed through surgery in Zhejiang Cancer Hospital and Zhejiang Provincial People′s Hospital from January 2013 to December 2023 were retrospectively collected.Based on defined criteria, FVPTC patients were categorized into high-invasion and low-invasion groups. The dataset was divided into a training set and a validation set in a ratio of 7 to 3. Clinical information and ultrasound feature parameters were collected. Univariate and multivariate Logistic regression analyses were performed on the training set. A predictive model for FVPTC invasiveness was constructed based on ultrasound features. The model′s discriminative ability and calibration were evaluated in the validation set, and a nomogram was generated.Results:The training set included a total of 218 patients with FVPTC, among which 131 were classified as high invasive.The validation set consisted of 94 patients, with 53 cases of high invasive FVPTC patients. Multivariate logistic regression analysis on the training set revealed that tumor multifocality ( OR=6.505, P=0.016), hypoechoic ( OR=3.235, P=0.103), shape ( OR=0.521, P=0.049), and microcalcifications ( OR=2.479, P=0.004) were independent influencing factors for predicting invasiveness in FVPTC. In the training set, the area under the curve (AUC) of the ultrasound predictive model was 0.704 (95% CI=0.634-0.771), and in the validation set, the AUC was 0.650 (95% CI=0.531-0.770), indicated good discriminative ability.The calibration curve showed good alignment with the ideal curve, demonstrating favorable calibration performance. Conclusions:Ultrasound features provide valuable information for assessing the invasiveness of FVPTC, and the model constructed by combining ultrasound features demonstrates good predictive efficacy for the invasiveness of FVPTC.

Objective:To compare the epidemiological and clinical characteristics of influenza A (IVA) and influenza B (IVB) in children of different ages, genders and seasons from 2016 to 2019.Methods:Retrospective analysis was performed on the children who were diagnosed as infected with influenza A and B virus in the outpatient and emergency department of Shanghai Eighth People′s Hospital from 2016 to 2019, including 2388 cases of influenza A virus infection and 1 575 cases of influenza B virus infection. The age, gender, time, characteristics of onset, and common indicators of blood routine tests were compared.Results:influenza virus infection is mostly prevalent from December to March of the next year, mainly influenza A virus, with minor epidemics from August to October of the next year, and influenza B virus from April to June of the next year. Compared with influenza B virus, children with respiratory tract infection caused by influenza A virus had higher WBC count, neutrophil, lymphocyte and monocyte abnormal proportions. The incidence rate of respiratory tract infection in the group infected with IVA was significantly higher ( P<0.05), and the incidence of infection in children among different age groups was significantly different ( P<0.05). Conclusions:The proportion of leukocyte and neutrophil increased, the lymphocyte was normal or decreased, and monocyte percentage increased in influenza A patients, which are more common than in influenza B patients, but the rate of abnormal increase of WBC was more common in influenza B cases. Children infected with influenza A are more likely to have anemia and platelet abnormality, and children with respiratory tract infection caused by the two viruses have different age groups. However, there was no significant difference between male and female.

OBJECTIVE： To study the effects of Atractylodes macrocephala ethanol extract （AM） on life span of Caenorhabditis elegans（called N 2 nematode for short ），and to investigate its mechanism based on transcription factor SKN- 1/ nuclear factor E 2 related factor 2（Nrf2）. METHODS ：N2 nematode were divided into blank control group ，positive control group （100 μ mol/L curcumin，similarly hereinafter ），AM low-dose ，medium-dose and high-dose groups （100，200，300 μ g/mL， similarly hereinafter ）. The effects of AM on the life span （by average survival time ）of N 2 nematode under normal condition and oxidant stress condition （40 mmol/L H 2O2）as well as its effects on reproductive capability （by the number of filial generation ）of N2 nematode under normal condition were investigated . 700 μmol/L H2O2 was used to establish neuroblastoma cells N 2a oxidant stress model. Effects of positive control ，low-dose，medium-dose and high-dose of AM on the survival rate of model cells were detected by MTT method. After human embryonic renalepithelial cells 293T were transfected with Nrf 2-ARE plasmid ， the effects of positive control and AM on luciferase activity of Nrf2-ARE were detected by luciferase reporter gene method at low，medium and high dose for 24 h and at medium dose for 12，18 and 24 h. RT-PCR was used to detect the effects ofpositive control ，low-dose，medium-dose and high-dose of AM on the mRNA expression of downstream genes NQO- 1 and HO- 1 of Nrf 2 in N 2a cells as well as mRN A expression of en@hactcm.edu.cn downstream genes GCS- 1，GST-7，GST-10，HSP-60，HSP- 16.2 and SOD- 3 of SKN- 1 in N 2 nematode. RESULTS ：Compared with blank control group ，average survival time of N 2 nematode under normal and oxidant stress condition was significantly prolonged in positive control group and AM groups ；the number of filial generation on the first day （except for AM high-dose group ），the number of filial generation on the second day （except for AM low-dose group ） and the total number of filial generation （except for AM low-dose group ） were increased significantly（P＜0.05 or P＜0.01）. The survival rate of N 2a cells in positive control group ，AM medium-dose and high-dose groups were significantly higher than that of model group （P＜0.05 or P＜0.01）. Compared with blank control group ，Nrf2-ARE luciferase relative activity of 293T cells in positive control group and AM groups as well as Nrf 2-ARE luciferase relative activity of 293T cells in AM medium-dose group after different time of treatment were increased significantly （P＜0.01），in dose-dependent and time-dependent trend. Compared with blank control group ，mRNA relative expression of HO- 1 and NQO- 1（except for positive control group ），GCS-1（except for AM low-dose group ），GST-7（except for positive control group and AM low-dose group ）， GST-10 and HSP- 60（except for AM low-dose group ），HSP-16.2（except for positive control group and AM low-dose group ）and SOD-3 （except for positive control group and AM low-dose group ） were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：AM can prolong the life span of N 2 nematode under normal and oxidant stress condition and improve the its reproductive capacity ，the mechanism of which may be associated with the activation of SKN- 1/Nrf2 signaling pathway.

Objective To investigate the role of CCAAT enhancer binding protein A (C/EBPα) in lung development by analyzing the relationship between dynamic expression of C/EBPα protein and cell differentiation in rat lung tissue.Methods According to the histological stages of rat lung development,lung tissues were collected on 15.5 d (the late pseudoglandular period),17.5 d (the canalicular period),19.5 d (the early saccular period) of embryonic age and at 12 h (the middle saccular period),on 4 d (the late saccular period),7 d (the alveolar period,the alveolar stage),14 d (the alveolar period,the equilibrium stage) of postnatal age.The lung morphologic appearance was observed by using HE staining.Western blot was used to detect the expressions of C/EBPα and surfactant Protein (SP)-A,SP-B,SP-C,SP-D.Phosphatidylcholine (PC) assay kit was utilized to analyze the secretion of PC.Periodic acid-schiff (PAS) staining was used to evaluate the amcunt of glycogen in lung tissue.Results (1) C/EBPαt and SP-A began to express on 15.5 d of embryonic age (0.36 ±0.02,0.01 ±0.01),while SP-B,SP-C and SP-D started to express on 17.5 d of embryonic age (0.33 ±0.06,0.01 ±0.01,0.11 ±0.08).All of them increased with the development of lung,and C/EBPα,SP-A,SP-C reached the highest level at 12 h of postnatal age (3.48 ±0.05,3.24 ± 0.19,1.26 ± 0.21),and SP-D on the postnatal 4 d (1.48 ± 0.10),then gradually decreased,while the expression of SP-B continued to rise.The levels of C/EBPα and SPs maintained stable on postnatal 14 d.The C/EBPα protein level was positively correlated with SPs at embryonic age of 15.5 d,17.5 d,19.5 d and postnatal age 12 h (r =0.999,0.991,0.982,0.951,all P ＜ 0.05).(2) The level of PC was very low at embryonic age of day 15.5 [(60.50 ± 1.30) μg/g].With the development of lung,the secretion of PC increased gradually,but there was no significant correlation between the expression of PC and C/EBPoα(all P ＞ 0.05).(3) The level of glycogen was high in the late pseudoglandular stage (15.5 d) (585.50 ± 2.20),the content of glycogen decreased with the development of lung,especially on the canalicular (embryonic day 17.5) and during early saccular period (embryonic day 19.5),and then it became stable during the alveolar period (postnatal age 7 d).The expression of C/EBPα had negative correlation with the content of glycogen in fetal lung(r =-1.000,P ＜ 0.01).Conclusion C/EBPα plays an important role in rat lung development,as it may promote lung maturation by regulating the synthesis and secretionof SPs and PC.

Objective To study the effects of propofol used alone and in combined with opioids in gastroscopy,in order to select the more suitable anesthesia protocol.Methods A total of 285 pa-tients undergoing gastroscopy were selected in April ,201 5 in our hospital,including 105 males,180 females,ranging from 18 to 65 years old,weighing 40-90 kg,falling the category of ASA Ⅰ or Ⅱ. According to random number table,subjects were divided into four groups:dezocine group(group D, n =76),fentanyl group (group F,n =87),oxycodone group (group O,n = 71 )and control group (group C,n =5 1).Each group was implemented the corresponding anesthesia.SBP,DBP,HR,SpO 2 in baseline(T0 ),1(T1 ),3(T2 ),5(T3 )min after entering gastroscope were recorded.Choking cough, body movement,extra propofol,awakening time and inspecting time were observed.Results Among four groups,there was no statistical significance in age,gender,weight,blood pressure,heart rate and oxygen saturation and other general information.There were more cases given extra propofol in group C than in the other three groups (P <0.01 ).While for the experimental groups,there were more cases needing extra propofol in group O than in group D and group F (P < 0.01 ).The incidences of body movement and choking cough in group C were higher than those in the other three groups (P <0.01 ).Compared with the group C,dosage of propofol ,awakening time in the three groups,especially in group D,were much lower (P < 0.01 ).Conclusion Propofol in combination with opioids for sedation during painless gastroscopy can alleviate adverse reaction caused by propofol used alone.The more suitable anesthesia protocol is propofol with dezocine.

Objective To evaluate the role of heparanase in endotoxemia-induced destruction of vascular endothelial glycocalyx in rats.Methods Forty-eight pathogen-free male Sprague-Dawley rats, aged 8-10 weeks, weighing 200-250 g, were randomly divided into 3 groups (n=16 each) using a random number table: control group (group C), lipopolysaccharide (LPS) group (group L) and LPS+ heparin group (group LH).Endotoxemia was induced by intravenous LPS 15 mg/kg in L and LH groups, and heparin sodium 100 U · kg-1 · h-1 was infused simultaneously in group LH.At 3 and 6 h after LPS injection, blood samples were collected from the femoral vein for determination of the serum concentrations of serum heparin sulfate (HS), syndecan-1, E-selectin and intercellular adhesion molecule-1 (ICAM-1) concentrations.The rats were then sacrificed, and lungs were removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio).Results Compared with group C, the serum HS, syndecan-1, E-selectin and ICAM-1 concentrations and W/D ratio were significantly increased in group L, and the serum HS and ICAM-1 concentrations were increased in group LH (P＜0.05).Compared with group L, the serum HS, syndecan-1, E-selectin and ICAM-1 concentrations and W/D ratio were significantly decreased in group LH (P＜0.05).The pathological changes of lungs were obvious in group L, and were significantly mitigated in group LH.Conclusion Heparanase is involved in endotoxemiainduced destruction of vascular endothelial glycocalyx in rats.

Objective To compare the effects of ephedrine and phenylephrine on hemodynamics in the patients undergoing surgery in prone position under general anesthesia.Methods Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 20-60 yr, with body mass index of 18.5-2:5.0 kg/m2, scheduled for elective posterior lumbar interbody fusion under general anesthesia, were randomized to ephedrine group (group E, n =30) or phenylephrine group (group P, n =30).When hypotension [decrease in systolic blood pressure (SBP) ＞20％ of the baseline value, T0] occurred in supine position, SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), cardiac index (CI) and central venous pressure (CVP) were recorded, and ephedrine 0.1 mg/kg (group E) or phenylephrine 1 μg/kg (group P) was injected via the central veins.The parameters mentioned above were recorded within 10 min after administration (T1-T10).Results Both ephedrine and phenylephrine could maintain the parameters of hemodynamics at the normal level.Compared with the baseline values at T0 , SBP, DBP, MAP and HR at T1-T10 and CO and CI at T2-T10 were significantly increased, and no significant change was found in CVP at each time point after administration in group E, and SBP and MAP at T1-T6, DBP at T1-T5, CVP at T2 and T3, and CO and CI at T1-T3 were significantly increased, and HR was decreased at T2 and T3 in group P.Compared with group P, SBP was significantly decreased at T1, and increased at T2-T10, DBP and MAP were decreased at T1, and increased at T3-T10, HR was increased at T1-T10, CO and CI were increased at T2-T10, and CVP was decreased at T1-T3 in group E.Conclusion Compared with phenylephrine, although ephedrine provides no significant effect on hemodynamics clinically, it can increase cardiac output to some extent in the patients undergoing surgery in prone position under general anesthesia.

Objective To compare the pressor responses to ephedrine during general anesthesia with different drugs.Methods Sixty ASA physical status Ⅰ or Ⅱ patients,scheduled for elective gastrointestinal tumor resection under general anesthesia,aged 20-64 yr,weighing 45-90 kg,were included in this study.The patients were randomized to receive dexmedetomidine + remifentanil + sevoflurane (group Ⅰ,n =20),propofol + remifentanil + sevoflurane (group Ⅱ,n =20),or dexmedetomidine + propofol + remifentanil + sevoflurane (group Ⅲ,n =20) to maintain the depth of anesthesia.Ephedrine 0.1 mg/kg was injected intravenously when the systolic blood pressure (SBP) was decreased to about 90 mm Hg during anesthesia.Blood pressure was monitored and recorded at 1-min intervals for 10 min after the injection.The onset time (TSBP,TDBP,TMAP) for ephedrine to raise the SBP,diastolic blood pressure (DBP) and mean arterial pressure (MAP) and the maximal amplitude (△SBP,△DBP,△MAP) were also recorded.Results Compared with Ⅱ group,TSBP,TDBP and TMAP were significantly shortened,and △SBP,△DBP and △MAP were increased in Ⅰ and Ⅲ groups (P ＜ 0.05).Conclusion Compared with propofol + remifentanil + sevoflurane combined anesthesia,dexmedetomidine + remifentanil + sevoflurane combined anesthesia and dexmedetomidine + propofol + remifentanil + sevoflurane combined anesthesia augment the pressor responses to ephedrine in patients.