Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.

Objective Olanzapine has a significant effect in the treatment of mental illness,so its use has been increasing year by year,and poisoning cases have occurred from time to time.Weight gain is a common side effect,and predicting it can be used as a warning to reduce the occurrence of olanzapine poisoning.In this paper,we screened out the differential metabolites between the olanzapine administration rats whose body weight significantly increased and no significantly changed weight.,therefore established an early diagnosis model for predicting olanzapine-induced weight gain in rats.Methods Thirty rats were randomly divided into the control group and olanzapine administration group,which were given continuously gavage with gthe normal saline and olanzapine for 28 days respectively.Blood was taken from the medial canthal vein on the first day after administration,and serum was collected for metabolomics analysis.The olanzapine group was divided into weight gain group and weight unchanged group by comparing with control group.The metabolic group data of the two groups were compared and the differential compounds were screened out between the two groups,Further then an early diagnosis model was established.Results There were 26 differential compounds between the weight gain group and the weight unchanged group after olanzapine administration for 28 days,including 10 lipids,which were involved in the metabolism of α-linolenic acid,the biosynthesis of unsaturated fatty acids,the biosynthesis of primary bile acids,and the synthesis of steroid hormones.Combined with the random forest algorithm,a early diagnosis model was established and the accurate rate was 80％.Conclusion Olanzapine administration would cause changes in the metabolome of rats,mostly concentrated in lipids,and the model based on 26 differential metabolites could be a candidate method for the early forensic determination of olanzapine poisoning.

Objective To investigate the significance of plasma levels of insulin-like growth factor(IGF)-1 and insulin-like growth factor binding protein(IGFBP)-3 in predicting acute respiratory distress syndrome(ARDS)and prognosis in critical patients.Methods A totally of 131 critical patients in intensive care unit(ICU)of the First Affiliated Hospital of Wenzhou Medical University were reviewed.Plasma concentrations of IGF-1,IGFBP-3,blood biochemistry,procalcitonin(PCT),lactic acid(LAC)and blood albumin were measured in enrolled patients.The 60-day fatality of enrolled patients was calculated.The differences between ARDS group and control group,as well as 60-day dead group and survival group were compared.Results Plasma IGF-1 and IGFBP-3 in ARDS group were significantly lower than those in control group,while plasma PCT was higher than that in control group.Plasma levels of IGF-1 and IGFBP-3 in dead group were significantly lower than those in survival group.Multivariate Logistic regression analysis and receiver operating characteristic curve results showed that IGF-1 area under curve(AUC)was 0.770,sequential organ failure assessment(SOFA)(AUC=0.692)and PCT(AUC=0.710)were independent risk factors for ARDS in critical patients.IGF-1(AUC=0.807),IGFBP-3(AUC=0.759)and SOFA score(AUC=0.859)were independent risk factors for death in critical patients.Conclusion The plasma levels of IGF-1 and IGFBP-3 in critica patients are significantly decreased,which may be an important factor for ARDS risk and fatality in critical patients.

Objective Olanzapine has a significant effect in the treatment of mental illness,so its use has been increasing year by year,and poisoning cases have occurred from time to time.Weight gain is a common side effect,and predicting it can be used as a warning to reduce the occurrence of olanzapine poisoning.In this paper,we screened out the differential metabolites between the olanzapine administration rats whose body weight significantly increased and no significantly changed weight.,therefore established an early diagnosis model for predicting olanzapine-induced weight gain in rats.Methods Thirty rats were randomly divided into the control group and olanzapine administration group,which were given continuously gavage with gthe normal saline and olanzapine for 28 days respectively.Blood was taken from the medial canthal vein on the first day after administration,and serum was collected for metabolomics analysis.The olanzapine group was divided into weight gain group and weight unchanged group by comparing with control group.The metabolic group data of the two groups were compared and the differential compounds were screened out between the two groups,Further then an early diagnosis model was established.Results There were 26 differential compounds between the weight gain group and the weight unchanged group after olanzapine administration for 28 days,including 10 lipids,which were involved in the metabolism of α-linolenic acid,the biosynthesis of unsaturated fatty acids,the biosynthesis of primary bile acids,and the synthesis of steroid hormones.Combined with the random forest algorithm,a early diagnosis model was established and the accurate rate was 80％.Conclusion Olanzapine administration would cause changes in the metabolome of rats,mostly concentrated in lipids,and the model based on 26 differential metabolites could be a candidate method for the early forensic determination of olanzapine poisoning.

Ex vivo-expanded mesenchymal stem cells(MSCs)have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative,multipotential,and immunomodu-latory capacities.However,the exact characteristics of MSCs remain largely unknown.By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton's jelly,we revealed five distinct subpopulations.The developmental trajectory of these five MSC subpopulations was mapped,revealing a differentiation path from stem-like active proliferative cells(APCs)to multipotent progenitor cells,followed by branching into two paths:1)unipotent preadipocytes or 2)bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent prechondro-cytes.The stem-like APCs,expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES,uniquely exhibited strong proliferation and stemness signatures.Remarkably,the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to sup-press activated CD3+T cell proliferation in vitro,supporting the role of this population in immunoregulation.In summary,our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation.Our findings advance the definition of MSCs by identifying the specific functions of their heteroge-neous cellular composition,allowing for more specific and effective MSC application through the purification of their functional subpopulations.

Objective:To investigate the preoperative ascending aorta diameter in patients with acute type A aortic dissection in the Chinese population, compares and analyze the differences in preoperative blood biomarkers, and evaluate the impact of the preoperative ascending aorta diameter in this part of patients on the short-term prognosis of patients.Methods:A collection of 641 patients with acute type A aortic dissection who were enrolled in the " Acute Aortic Syndrome High-Risk Early Warning and Intervention Study" project from January 2018 to January 2020 were collected. Divide the patients into two groups (group Ⅰ<55 mm, group Ⅱ≥55 mm) according to the preventive intervention value of ascending aorta diameter recommended by the guideline for studying preoperative ascending aorta diameter difference in blood biomarkers and the influence of ascending aorta diameter on the short-term prognosis of patients. All patients had CT scans to assess the diameter of the ascending aorta before operation.Results:In this study, all patients with acute type A aortic dissection had a mean preoperative ascending aorta diameter of (46.9±9.7)mm. The preoperative ascending aorta diameter of all patients was less than 55 mm, accounted for 84.1%. Male patients were more likely to have aortic dissection than females; most patients' age was less than 60 years old. The preoperative blood inflammatory index counts were higher in the ascending aorta diameter ≥55 mm group. However, the long-term prognosis of patients with different ascending aorta diameters before surgery was not apparent in this study. The preoperative survival rate and short-term survival rate of patients with ascending aorta diameter <55 mm were higher than those of other groups, but the difference was not statistically significant.Conclusion:In patients with acute type A aortic dissection, the diameter of the ascending aorta is usually less than 55 mm. Moreover, the blood inflammatory index counts are high in the preoperative ascending aorta diameter ≥55 mm group. Meanwhile, patients with smaller ascending aorta diameter have better survival rate and short-term prognosis.

It introduced the definition of the caregiver and at home and abroad,and also reviewed influencing factors of family caregiver′s burden of the elderly patients. At last, it put forward the essentiality to perfect the nursing intervention and improve caregivers' coping capacity, as well as the transitional care model and the linkage"hospital-community-family",and improve national legislation and policy support in order to structure the social support system at the same time, so as to provide reference for study of reducing the family caregiver′s burden of the elderly patients.

Objective To explore the experience of the family caregivers of the old hip fracture patients with cognition impairment. Methods By using purpose sampling method,11 participants which treating from January to April 2017 were applied semi-structured in-depth interview,and then analysis the material. Results Four themes were analyzed about the caring demands of the family caregivers, including existing heavier caring burden,inadequate knowledge and skills,positive face to the caring task, desire to caregiver support system. Conclusions The family caregivers of the old hip fracture patients with cognition impairment exist heavier caring burden, the medical service institutions should call on national policy support and economic aid for caregivers, care about the mental health of caregivers and improve their coping ability, as well as provide professional knowledge and skills guidance and build a perfect caregiver support system at the same time in order to reduce the burden of caregivers early.

Background and purpose:Drug resistance is a major cause of failure in lung cancer chemotherapy. This study aimed to investigate the effect of YAP on doxorubicin resistance in lung cancer and its underlying mechanism. Methods:Doxorubicin resistant lung cancer cell clones were established from parental sensitive cancer PC9 cell line via in vitroinduction, and the expression of YAP was analyzed. YAP was down-regulated via shRNA to different levels. MTS assay was employed to determine cell proliferation and drug sensitivity. Flow cytometry was used to determine cell cycle distribution, apoptosis and uptake of Rh-123. Western blot and quantitative real-time polymerase chain reaction (QRT-PCR) assay were used to determine the expression of ABCB1, ABCC1, p53, Runx2, ITGB2 and ErbB4. The phosphory-lation of serine/threonine kinase (AKT) was determined as well.Results:Doxorubicin resistant PC9/Adr cell clone was obtained with over-expressed YAP. Expression of YAP in PC9/Adr cells was down-regulated to different levels via shR-NA. After YAP silencing, cell proliferation was reduced, while sensitivity to doxorubicin was increased. The cell cycle was significantly halted by G0/G1 phase. Doxorubicin induced-apoptotic rate and cellular uptake of Rh-123 were increased,with positive correlation to YAP silencing level. Western blot and QRT-PCR results showed that after YAP silencing, ABCB1, ABCC1, Runx2, ITGB2, and ErbB4 proteins were down-regulated, while the expression of p53 was up-regulated. Phosphorylation of AKT was inhibited as well.Conclusion:Over-expression of YAP is involved in doxorubicin resistance in PC9/Adr cell line. Silencing of YAP could restore doxorubicin sensitivity. The mechanism involves regulation of drug resistance-related genes and promotion of apoptosis.

Objective To explore the effect on traditional experiment and case teaching method in regional anatomy study. Methods 80 students from 2014 medical students were randomly selected as the teaching subjects and divided into traditional group and case teaching group. The traditional group con-tained 40 students, using the traditional teaching method, while case teaching group had also 40 students with case teaching method. In the process of teaching, three clinical cases were introduced, including thesubtotal thyroidectomy thoracic outlet syndrome andpancreatic cancer. After the end of the course, the students conducted a unified questionnaire and examination. SPSS 18.0 was used for data line t test or chi square test between the two groups. Results The scores of the students in the case group in the selection questions, blanks and essay questions in the final exam were higher than those of the traditional group; The average total score of the case group was (85.69 ±11.61), while the traditional group was (73.19 ±18.66), and the difference was statistically significant (t=3.597, P=0.002). The results of the questionnaire showed that the students in the case group were higher than the traditional group, and the difference was statistically significant ( χ2=14.753, P=0.001). Conclusion The effect on regional anatomy study with case teaching method is better than the traditional teaching method, and it is a promising teaching reform for the med-ical students.