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 evaluate the safety and efficacy of using small and ultra-small sized grafts for in situ auxiliary liver transplantation in the treatment of portal hypertension.Methods:A prospective single-arm cohort study was conducted. Patients who underwent liver transplantation at Beijing Friendship Hospital from December 2014 to July 2025 were included. Intraoperative portal vein pressure was routinely monitored, with the target regulation for portal vein blood flow set at<15 mmHg (1 mmHg=0.133 kPa) and follow-up continued until September 2025. The primary endpoints were the patient's status and graft survival. The secondary endpoints were small-for-size syndrome and perioperative complications. The small-for-size syndrome was graded according to the 2023 International Liver Transplantation Society consensus statement.Results:A total of 33 cases were enrolled. Among them, 22 had ultra-small size grafts, 11 had small-size grafts, 28 had living donor grafts, and five had split grafts. The graft-to-recipient weight ratio in living donor liver transplantation was 0.31%～0.79%, while in split liver transplantation it was 0.45%～1.02%. Intraoperative portal vein pressure of ≥15 mmHg was observed in 11 cases, who underwent portal vein blood flow adjustment via splenic artery ligation (2 cases), partial splenectomy (8 cases), and/or restrictive portocaval shunting (1 case), after which all patients achieved the target portal vein pressure. All cases completed at least one month of follow-up, with 28 cases following for more than one year, and the median follow-up period was 36.5 months. Early-stage postoperative small-for-size syndrome occurred in eight cases (24.2%, 8/33), all classified as grade A, with improvements following supportive treatment. Severe complications (Clavien-Dindo≥Ⅲ) occurred in three cases (9.1%, 3/33). The one-year survival rate was 92.9% (26/28). The overall survival rate at the end of follow-up was 90.9% (30/33). No patients experienced graft loss or death due to small-for-size syndrome. Graft tissue tested negative for hepatitis B core antibody and covalently closed circular DNA, and hepatitis B surface antigen seroconversion was achieved following second-stage residual liver resection and under a combined strategy of potent nucleos(t)ide analogs and hepatitis B immunoglobulin in ten cases of hepatitis B-related disease.Conclusions:With standardized portal vein blood flow monitoring and individualized portal vein blood flow adjustment, in situ auxiliary liver transplantation can safely and effectively use small and even ultra-small sized grafts, thereby significantly expanding graft sources and ensuring donor and recipient safety. These findings warrant further validation and promotion in multicenter controlled studies.

Objective:To investigate whether there is an association between the total dose of breast cancer radiotherapy, the mean dose of radiation field involving the heart and its substructures, and the long-term incidence of coronary heart disease (CHD) in patients.Methods:A retrospective analysis was conducted on 1125 patients with breast cancer who received radiotherapy with radiation fields involving the hear at Beijing Hospital from January 2009 to June 2022. The heart and its substructures of 54 patients were manually delineated, trained an automatic delineation model, and applied this model to the original radiotherapy planning images to automatically extract dosimetric parameters for the heart and substructures in the original plan. Based on the follow-up results, 1125 breast cancer patients were categorized into the CHD event group ( n=19) and non-event group ( n=1106). Wilcoxon rank-sum test, Chi-square test and adjustment for confounding factors using inverse probability weighting were used to compare the mean radiation dose received by the heart and its substructures, age at presentation, history of smoking, history of alcohol consumption, history of hypertension, and history of diabetes between two groups. The influencing factors of CHD were analyzed by univariate and multivariate logistic regression models. Results:The mean heart dose ( P=0.035), mean dose of right atrium ( P=0.049), right coronary artery ( P=0.013), septum ( P=0.045), and right ventricle ( P=0.039) of the event group were higher than that of the non-event group, and the differences were statistically significant. History of alcohol consumption was an independent risk factor for long-term CHD events in the breast cancer patients ( OR=7.35,95% CI: 1.56-25.58, P=0.004). After adjusting for confounding factors using inverse probability weighting, age at presentation was an independent risk factor for long-term CHD events ( OR=1.03, 95% CI: 1.01-1.05, P=0.004). Conclusions:In the breast cancer population with traditional high-risk factors of CHD receiving radiotherapy, the possibility of CHD probably remains high even if the dose of radiation field involving the heart and its substructures is low. Compared to traditional risk factors of CHD, the mean dose to the heart and its substructures in the radiation field of breast cancer patients exerts less impact on the occurrence of CHD after radiotherapy.

The aim of this study is to explore the immunogenicity of African swine fever virus p37 recombinant protein in mice.C57BL/6J mice were immunized subcutaneously in the abdomen using p37 recombinant protein as antigen.The second immunization was performed 21 d after the first immunization.Serum-specific antibody levels were detected by ELISA;serum cytokine levels were detected using a multifactor assay technique;mice splenic lymphocytes were isolated 7 d after sec-ondary immunization,and the number of splenic lymphocytes secreting IFN-γ after recombinant protein stimulation was detected by ELISpot;and the ratio of CD4+T cells to CD8+T cells was detected by flow cytometry.The results of indirect ELISA showed that p37 recombinant protein could stimulate mice to produce high levels of specific antibodies;ELISpot showed that p37 recom-binant protein could significantly stimulate splenic lymphocytes to produce IFN-γ(P＜0.001)and activate cellular immune responses;the results of flow cytometry showed that it could signifi-cantly stimulate the differentiation of T-lymphocytes to CD4+T-lymphocytes(P＜0.001).In ad-dition,serum levels of IL-2,IL-4,IFN-γ,and TNF-α immune-related cytokines were significantly higher after the second immunization.Immunization of mice with p37 recombinant protein induced strong humoral and cellular immune responses with good immunogenicity,providing reference for the subsequent epitope identification and functional study of p37 protein and the antigen screening of ASF mRNA vaccine.

In order to establish a highly efficient,convenient,and effective circular RNA(circRNA)vaccine preparation system,enhanced green fluorescent protein(EGFP)circRNA was constructed using permuted intron exon(PIE)strategy based on type Ⅰ introns.Then,circRNA circularization rates of RNA after in vitro transcription(IVT),primary circularization(IVC1),and secondary circularization(IVC2)were compared after purification.The constructed circRNA system was fur-ther applied to porcine reproductive and respiratory syndrome virus(PRRSV),and two circRNAs based on PRRSV GP5 protein were constructed and developed for in vitro expression.Results showed that circularization rates and protein expression effects of EGFP circRNA in IVC1 RNA and IVC2 RNA were similar,but both were significantly better than those of IVT RNA.Purity of EGFP circRNA reached 74％,and purities of two PRRSV GP5 protein circRNAs constructed using this preparation system were 71％and 64％,respectively.Western blot and indirect immunofluo-rescence assay(IFA)results indicated that both of the PRRSV GP5 protein circRNAs were suc-cessfully expressed.The results demonstrated that an easy-to-operate,low-cost circRNA prepara-tion system with high circularization rate was successfully constructed.Two PRRSV GP5 protein circRNA vaccines were successfully prepared using this system and expressed efficiently,which provides a reference for the development of animal circRNA vaccines and novel candidate vaccines against PRRSV.

Objective:To explore the longitudinal predictive relationship between self-neglect and frailty among older adults.Methods:Data were drawn from the Chinese Longitudinal Healthy Longevity Survey conducted in 2011 (T1), 2014 (T2), and 2018 (T3). A total of 1 495 older adults aged≥65 years at T1 who participated in three consecutive surveys and had no missing key variables were included. General demographic information, self-neglect scores, and frailty status were extracted. Spearman correlation analysis was used to examine the association between self-neglect and frailty. Cross-lagged analysis was employed to investigate the potential causal relationship between the two variables.Results:The self-neglect scores for 1 495 older adults at T1, T2, and T3 were (2.84±1.39), (2.47±1.30), and (2.41±1.20), respectively, showing a declining trend. The frailty scores at T1, T2, and T3 were 0 (0, 1.00), 0 (0, 2.00), and 1.00 (0, 2.00), respectively, indicating an increasing trend. Cross-lagged analysis revealed that self-neglect at T1 positively predicted frailty at T2 (β=0.076, P=0.004). Frailty at both T1 and T2 positively predicted self-neglect at T2 (β=0.057, P=0.044) and T3 (β=0.058, P=0.029), respectively. Conclusions:Frailty among older adults positively predicts self-neglect, and self-neglect also has a certain predictive effect on frailty. Medical staff should strengthen early screening and intervention for frailty in older adults to delay the occurrence and progression of self-neglect.

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 explore the longitudinal predictive relationship between self-neglect and frailty among older adults.Methods:Data were drawn from the Chinese Longitudinal Healthy Longevity Survey conducted in 2011 (T1), 2014 (T2), and 2018 (T3). A total of 1 495 older adults aged≥65 years at T1 who participated in three consecutive surveys and had no missing key variables were included. General demographic information, self-neglect scores, and frailty status were extracted. Spearman correlation analysis was used to examine the association between self-neglect and frailty. Cross-lagged analysis was employed to investigate the potential causal relationship between the two variables.Results:The self-neglect scores for 1 495 older adults at T1, T2, and T3 were (2.84±1.39), (2.47±1.30), and (2.41±1.20), respectively, showing a declining trend. The frailty scores at T1, T2, and T3 were 0 (0, 1.00), 0 (0, 2.00), and 1.00 (0, 2.00), respectively, indicating an increasing trend. Cross-lagged analysis revealed that self-neglect at T1 positively predicted frailty at T2 (β=0.076, P=0.004). Frailty at both T1 and T2 positively predicted self-neglect at T2 (β=0.057, P=0.044) and T3 (β=0.058, P=0.029), respectively. Conclusions:Frailty among older adults positively predicts self-neglect, and self-neglect also has a certain predictive effect on frailty. Medical staff should strengthen early screening and intervention for frailty in older adults to delay the occurrence and progression of self-neglect.

The aim of this study is to explore the immunogenicity of African swine fever virus p37 recombinant protein in mice.C57BL/6J mice were immunized subcutaneously in the abdomen using p37 recombinant protein as antigen.The second immunization was performed 21 d after the first immunization.Serum-specific antibody levels were detected by ELISA;serum cytokine levels were detected using a multifactor assay technique;mice splenic lymphocytes were isolated 7 d after sec-ondary immunization,and the number of splenic lymphocytes secreting IFN-γ after recombinant protein stimulation was detected by ELISpot;and the ratio of CD4+T cells to CD8+T cells was detected by flow cytometry.The results of indirect ELISA showed that p37 recombinant protein could stimulate mice to produce high levels of specific antibodies;ELISpot showed that p37 recom-binant protein could significantly stimulate splenic lymphocytes to produce IFN-γ(P＜0.001)and activate cellular immune responses;the results of flow cytometry showed that it could signifi-cantly stimulate the differentiation of T-lymphocytes to CD4+T-lymphocytes(P＜0.001).In ad-dition,serum levels of IL-2,IL-4,IFN-γ,and TNF-α immune-related cytokines were significantly higher after the second immunization.Immunization of mice with p37 recombinant protein induced strong humoral and cellular immune responses with good immunogenicity,providing reference for the subsequent epitope identification and functional study of p37 protein and the antigen screening of ASF mRNA vaccine.

In order to establish a highly efficient,convenient,and effective circular RNA(circRNA)vaccine preparation system,enhanced green fluorescent protein(EGFP)circRNA was constructed using permuted intron exon(PIE)strategy based on type Ⅰ introns.Then,circRNA circularization rates of RNA after in vitro transcription(IVT),primary circularization(IVC1),and secondary circularization(IVC2)were compared after purification.The constructed circRNA system was fur-ther applied to porcine reproductive and respiratory syndrome virus(PRRSV),and two circRNAs based on PRRSV GP5 protein were constructed and developed for in vitro expression.Results showed that circularization rates and protein expression effects of EGFP circRNA in IVC1 RNA and IVC2 RNA were similar,but both were significantly better than those of IVT RNA.Purity of EGFP circRNA reached 74％,and purities of two PRRSV GP5 protein circRNAs constructed using this preparation system were 71％and 64％,respectively.Western blot and indirect immunofluo-rescence assay(IFA)results indicated that both of the PRRSV GP5 protein circRNAs were suc-cessfully expressed.The results demonstrated that an easy-to-operate,low-cost circRNA prepara-tion system with high circularization rate was successfully constructed.Two PRRSV GP5 protein circRNA vaccines were successfully prepared using this system and expressed efficiently,which provides a reference for the development of animal circRNA vaccines and novel candidate vaccines against PRRSV.