TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.

Objective:To explore the attitudes of Chinese medical students toward the elderly and their willingness to practice in geriatrics, and to investigate the influence of geriatrics education on their attitudes.Methods:Medical students studying diagnostics in four medical universities were enrolled in a cross-sectional survey and, for the intervention study, graduate trainees from non-geriatrics specialties taking a geriatrics course were interviewed before and after the course.An electronic questionnaire was used to collect general information, the experience of interacting with the elderly, attitudes towards the elderly and the willingness to develop careers in geriatric medicine.Changes in attitudes towards the elderly and their willingness to practice in geriatrics before and after the 40-hour geriatric medicine course were compared.Results:A total of 648 medical students completed the cross-sectional survey, with the highest score in compassion for the elderly(3.54±0.54)and the lowest score for medical services for elderly patients(3.36±0.78). Only 2.2%(14/648)of the students showed strong interest in geriatric medicine.The results of the intervention from 42 graduate trainees showed that the average scores of revised Geriatric Attitude Scale(r-GAS)were 3.80±0.43 and 3.92±0.40 before and after the course, respectively, and the difference was statistically significant( t=2.148, P=0.038). At the end of the course, 7 trainees(16.7%, 7/42)showed great interest in geriatrics, significantly different from 2 trainees(4.8%, 2/42)before the course( χ2=8.211, P=0.025). Conclusions:Chinese medical students show a serious lack of interest in geriatrics, and geriatrics education can improve their attitudes towards the elderly and their willingness to work in geriatrics.With the rapid population aging in China, it is urgent to strengthen the education of geriatric medicine.

OBJECTIVE To investigate the genes of disinfectant-sulfadiazine and antibiotic resistance of Escherichia coli strains in elderly wards.METHODS Polymerase chain reaction and dilution test were used to detect and analyze the disinfectant-sulfadizane drug resistance gene and drug resistance of the E.coli.RESULTS From 30 E.coli strains isolated from elderly patients,21 were detected carrying disinfectant-sulfadizine drug resistance genes,and the positive rate of qacE△1-sulⅠ was 70.0%.CONCLUSIONS The detection rate of disinfectant-sulfadiazine drug resistance gene from E.coli strains isolated from elderly patients,the bacteria detection rates are relatively high.Most of the isolates were resistant to commonly used antibiotics.It suggests that clinical drug-resistant strains may be resistant to disinfectants.This condition should be paid much attention by disinfection wotkers of our country.

Objective To determine the effects of dibutyl phthalate(DBP) on female mice reproductive system. Methods The healthy Kunming adult female mice with body weight from 22 g to 30 g were randomly divided into 4 groups,one as reagent control group. The other three as treated groups, 12 female mice per group. In the exposure groups,the mice were administrated by peritoneal injection with DBP at the dose of 400?40?4mg/kg body weight,respectively. The mice in control group were administrated with the same amount of vehicle(dimethyl sulfoxide). All the mice were administrated once a day,continuously for 14 days. The estrous cycles were observed during the period of the experimental study. On the fifteenth and twenty-eightieth days,the mice were sacrificed. The organ coefficients of uterus and ovary were determined,and the histopathological changes of the left ovary were observed. Results The estrous cycles in 400 mg/kg body weight dose group and 40 mg/kg body weight dose group were markedly delayed with a significant dose-effect relationship. The organ coefficients of the uterus in the groups exposed to DBP were significantly higher than that of the control group. On the fifteenth days,the number of mature follicles in 400 mg/kg body weight dose group was less than that of the control group,but the number of atretic follicles in 400 mg/kg body weight dose group and 40 mg/kg body weight dose group were more than that of the control group. On the twenty-eightieth days,the number of atretic follicles in 400 mg/kg body weight dose group was more than that of the control group. Conclusion Dibutyl phthalate had adverse effects on the reproduction-endocrine system of adult female mice. DBP might demonstrate an estrogenic activity in vivo.