Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Objective: To explore the assocation of the family environment and depressive symptoms among primary and middle school students, so as to provide suggestions for further maximizing the utility of family environment in the growth of primary and secondary school students, as well as prevention and intervention of depressive symptoms among children and adolescents. Methods: From June to July 2024, through a multistage cluster random sampling method, 8 800 primary and middle school students aged 10 to 18 from 36 schools in 3 cities (Datong, Lvliang, Linfen) in Shanxi Province. A self designed questionnaire was used to conduct a family environment survey, including family socioeconomic conditions, family structure, family parenting behavior, family member health behavior, etc; and the depression symptoms of primary and secondary school students were investigated by Patient Health Questionnaire-9. The χ 2 test and binary Logistic regression to method were used to analyze the association of the family environment with depressive symptoms among primary and secondary school students, and to analyze gender and urban-rural heterogeneity in this association. Results: The detection rate of depressive symptoms among primary and middle school students was 46.7% ( n = 4 111 ). Among them, the detection rates of depressive symptoms for male and female students were 45.7% and 47.7% respectively, and the detection rates for rural and urban students were 48.0% and 44.9% respectively. The results of binary Logistic regression model showed that in the family environment, factors such as the father s education level (junior high school: OR =0.84), self assessed family socio economic status (average: OR =0.78, good: OR =0.80), parental support and understanding (yes: OR = 0.55 ), family atmosphere (harmonious: OR =0.66), living arrangement (living only with father or mother: OR =1.31, living with parents and grandparents: OR =1.19), and family rearing style (combining punishment and reward: OR =1.42, punishment only: OR =1.25) were related to depressive symptoms in primary and middle school students in Shanxi Province ( P <0.05). From the perspective of gender heterogeneity, the living arrangement (living only with father or mother: OR =1.67, others: OR =1.67) had a statistically significant association with depressive symptoms in male students ( P <0.05). From the perspective of urban rural heterogeneity, the living arrangement (living only with father or mother: OR =1.38) had a statistically significant association with depressive symptoms in rural primary and middle school students ( P <0.05). Conclusions The family environment has an important impact on depressive symptoms in primary and middle school students. Family functioning should be fully exerted to prevent depressive symptoms in primary and middle school students.

To explore the interaction between ASFV capsid protein M1249L and host from the host cellular perspective,M1249L was selected for constructing the bait plasmid(pGBKT7-M1249L)to screen the bone marrow-derived macrophages(BMDMs)cDNA library.After again co-transform and sequence alignment,20 candidate interacting host proteins were screened,such as IL-1β,CTSB and DNAJA3.And then,co-immunoprecipitation assay was performed to verify the interaction be-tween M1249L and host proteins.GO ontology(GO)and KEGG pathway enrichment analyses re-vealed that biological regulation,cellular communication and response to stimulus and others were enriched in biological processes.And these host proteins could share some pathways,including toll-like receptor signaling pathway and Nod-like receptor signaling pathway.Therefore,the results provides the theoretical basis for further research on the mechanism of ASFV M1249L in viral in-fection and immune regulation.

Objective To investigate the relationship between serum IL-8,homocysteine(Hey),C-reactive protein(CRP)levels and severity of coronary lesions in patients with coronary heart disease(CHD)complicated by chronic heart failure(CHF),as well as their prognostic value.Methods A total of 118 elderly eligible patients admitted to our hospital from January 2023 to September 2024 were prospectively recruited,and according to their Gensini score,they were divided into mild,moderate and severe stenosis groups(45,50 and 23 cases,respectively).Accord-ing to the clinical outcomes after follow-up,they were divided into a good prognosis group(82 cases)and a poor prognosis group(36 cases).The serum levels of IL-8,Hcy and CRP were com-pared among the three groups of different stenosis,and Pearson correlation analysis was used to examine the relationship between the three indicators and the severity of coronary lesions.Cox regression analysis was performed to identify factors influencing poor prognosis in patients with CHD and CHF,and receiver ROC curve analysis was conducted to assess the diagnostic value of serum IL-8,Hey,and CRP levels in predicting prognosis.Results The serum levels of IL-8,Hey and CRP were gradually decreased in the severe,moderate and mild stenosis groups in turn,with statistical significances(P＜0.05).Pearson correlation analysis indicated that serum IL-8,Hcy,and CRP levels were positively correlated with the severity of coronary lesions in the patients with CHD and CHF(r=0.364,0.355,0.372,P＜0.01).Significant differences were found in age,NT-proBNP,D-D,IL-8,Hcy,and CRP levels between the good and poor prognosis groups(P＜0.05).Cox regression analysis revealed that age,NT-proBNP,D-D,IL-8,Hcy,and CRP were influencing factors for poor prognosis in patients with CHD and CHF(P＜0.05).ROC curve ana-lysis showed that the AUC value of IL-8,Hey,CRP,and their combination in predicting prognosis was 0.698,0.714,0.723 and 0.899,respectively.Conclusion In the patients with CHD and CHF,serum IL-8,Hcy,and CRP levels are associated with the severity of coronary lesion and prognosis.Moreover,combining these three indicators has significant diagnostic value for predicting patient outcomes.

To explore the interaction between ASFV capsid protein M1249L and host from the host cellular perspective,M1249L was selected for constructing the bait plasmid(pGBKT7-M1249L)to screen the bone marrow-derived macrophages(BMDMs)cDNA library.After again co-transform and sequence alignment,20 candidate interacting host proteins were screened,such as IL-1β,CTSB and DNAJA3.And then,co-immunoprecipitation assay was performed to verify the interaction be-tween M1249L and host proteins.GO ontology(GO)and KEGG pathway enrichment analyses re-vealed that biological regulation,cellular communication and response to stimulus and others were enriched in biological processes.And these host proteins could share some pathways,including toll-like receptor signaling pathway and Nod-like receptor signaling pathway.Therefore,the results provides the theoretical basis for further research on the mechanism of ASFV M1249L in viral in-fection and immune regulation.

Objective To investigate the relationship between serum IL-8,homocysteine(Hey),C-reactive protein(CRP)levels and severity of coronary lesions in patients with coronary heart disease(CHD)complicated by chronic heart failure(CHF),as well as their prognostic value.Methods A total of 118 elderly eligible patients admitted to our hospital from January 2023 to September 2024 were prospectively recruited,and according to their Gensini score,they were divided into mild,moderate and severe stenosis groups(45,50 and 23 cases,respectively).Accord-ing to the clinical outcomes after follow-up,they were divided into a good prognosis group(82 cases)and a poor prognosis group(36 cases).The serum levels of IL-8,Hcy and CRP were com-pared among the three groups of different stenosis,and Pearson correlation analysis was used to examine the relationship between the three indicators and the severity of coronary lesions.Cox regression analysis was performed to identify factors influencing poor prognosis in patients with CHD and CHF,and receiver ROC curve analysis was conducted to assess the diagnostic value of serum IL-8,Hey,and CRP levels in predicting prognosis.Results The serum levels of IL-8,Hey and CRP were gradually decreased in the severe,moderate and mild stenosis groups in turn,with statistical significances(P＜0.05).Pearson correlation analysis indicated that serum IL-8,Hcy,and CRP levels were positively correlated with the severity of coronary lesions in the patients with CHD and CHF(r=0.364,0.355,0.372,P＜0.01).Significant differences were found in age,NT-proBNP,D-D,IL-8,Hcy,and CRP levels between the good and poor prognosis groups(P＜0.05).Cox regression analysis revealed that age,NT-proBNP,D-D,IL-8,Hcy,and CRP were influencing factors for poor prognosis in patients with CHD and CHF(P＜0.05).ROC curve ana-lysis showed that the AUC value of IL-8,Hey,CRP,and their combination in predicting prognosis was 0.698,0.714,0.723 and 0.899,respectively.Conclusion In the patients with CHD and CHF,serum IL-8,Hcy,and CRP levels are associated with the severity of coronary lesion and prognosis.Moreover,combining these three indicators has significant diagnostic value for predicting patient outcomes.

Objective:To investigate the longitudinal relationship between solution-focused thinking and de-pressive symptoms in college students.Methods:A total of 261 college students were assessed with the Solution-Fo-cused Inventory(SFI)and Self-rating Depression Scale(SDS)in a 3-month interval.Data were analyzed with re-petitive measures analysis of variance and the cross-lagged panel model.Results:The detection rates for depressive symptoms at baseline and 3-month laterwere 39.46％and 47.89％,respectively.The scores of problem disengage-ment showed decrease after 3 months(P＜0.01).In the cross-lagged model,the baseline scores of SFI could signif-icantly predict the decrease in scores of SDS after 3 months(β=-0.19,P＜0.05),while the baseline scores of SDS could not predict the scores of SFI after 3 months(β=-0.05,P＞0.05).Conclusion:The findings suggest that solution-focused thinking may alleviate depressive symptoms.

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

Objective To observe the effect of preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer on lung function and mRNA expression of GATA-binding protein 3(GATA3)and forkhead protein P3(Foxp3)in peripheral blood.Methods Sixty esophageal cancer patients who underwent modified Ivor-Lewis surgery in our hospital from January 2022 to October 2023 were selected and divided into two groups by simple random method.The control group was given conventional diet before operation,and the observation group was given enteral nutrition support before operation.The two groups were compared in terms of nutritional support.Results Both groups showed significantly decreases in one-second exertion expiratory volume/exertion lung volume(FEV1/FVC)(P<0.05),FVC(P<0.05),FEV1(P<0.05)and the levels of peripheral blood GATA3(P<0.05),Foxp3 mRNA(P<0.05)expression compared with those at admission(P<0.05),but no significant differences in pulmonary function(P>0.05),peripheral blood GATA3(P>0.05),and Foxp3 mRNA(P>0.05)expression between them at 1 week postoperatively.Both groups exhibited significantly lower levels of albumin,prealbumin,haemoglobin,transferrin,PNI and body mass and body mass index at admis-sion as compared to those at one week after surgery(P<0.05).The observation group showed significantly higher levels of albumin,prealbumin,haemoglobin,transferrin,and PNI at 1 week postoperatively(P<0.05),but no significant differences in ventilation time,defecation time,drain retention time,hospitalisation time,and compli-cation rate as compared to the control group(P>0.05).Conclusion Preoperative enteral nutritional support combined with modified Ivor-Lewis surgery for esophageal cancer improves postoperative nutritional status,and ren-ders less effect on postoperative lung function and peripheral blood GATA3 and Foxp3 mRNA expression.