Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective:To develop a health behavior guidance program for stroke rehabilitation patients based on the adaptive leadership framework (ALF) .Methods:Relevant stroke health behavior guidelines were systematically retrieved, screened, included, and recommendations extracted from domestic and international websites. The initial draft of the health behavior guidance program for stroke rehabilitation patients was developed in light of the ALF. From January to March 2022, the draft was refined through two rounds of Delphi expert consultation, resulting in the finalized health behavior guidance program.Results:A total of 10 guidelines were included, and 73 guideline recommendations were extracted. These recommendations were categorized into six dimensions and 25 specific items. In both rounds of expert consultation, 15 questionnaires were distributed and all were returned, yielding an effective recovery rate of 100.00%, with an expert authority coefficient greater than 0.8. Based on expert feedback and group discussions, the final program included eight dimensions and 31 items, adding sleep management and regular health consultations to the original six dimensions.Conclusions:The health behavior guidance program for stroke rehabilitation patients, based on the ALF, introduces a new perspective on nursing by reasonably dividing adaptive and technical problems. This approach aligns with clinical practice in China, providing scientific and practical value for promoting health behaviors and offering a new perspective for health education in stroke patients.

Blood screening is essential for blood safety. Traditional methods are not very effective in unknown pathogen testing. The blood metagenomic analysis with high-throughput sequencing as the main method is not limited to a particular microbe but detects all microbes in the sample (total genome), which has advantages that traditional methods cannot compare with. With the increasingly maturation of technology and the gradual reduction of cost, metagenomic sequencing has been applied more and more widely. In this paper, the concept and research procedures of metagenomics, the current status and future prospect of metagenomics sequencing technology in the field of blood screening are reviewed.

AIM: To investigate the effect of autophagy on cell ferroptosis in intestinal ischemia-reperfusion injury. METHODS: Twenty-four SPF grade Wistar rats weighing 200-220 g were divided into 4 groups (n = 6): sham operation group (sham group), ischemia group (I group), ischemia-reperfusion group (I/R group),and ischemia-reperfusion + autophagy inhibitor group (I/R + 3-MA group). The ischemia model was established by clamping the superior mesenteric artery for 1 hour, and the intestinal ischemia-reperfusion injury model was established by reperfusion for 2 hours. HE staining was used to observe the pathological changes of intestinal mucosa and Chiu score under light microscope. Fe

【Objective】 To detect the anti-SARS-CoV-2 antibody levels in blood donors in Guangzhou, so as to provide laboratory data support for the collection and clinical use of convalescent plasma. 【Methods】 Anti-SARS-CoV-2 antibodies were measured by ELISA in qualified donors. Among them, 326 donors who gave blood in February 2023 were tested for IgG antibodies, 444 donors were tested for neutralizing antibodies. In July 2023, 398 donors were tested for IgG and IgM. 【Results】 399 of 724 blood samples diluted with normal saline (1∶160) were IgG reactive, with a reactive rate of 55.11%. Chi-square test showed that there was a significant difference in the reactive rate of IgG among samples collected at different times (25.46% in February vs 79.40% in July, χ²=210.74, P<0.01, 95%CI: 7.97, 15.98), but there was no significant difference in the reactive rate between different genders and different age groups. IgM was detected in 5 of 398 blood samples, with a reactive rate of 1.26%. The IgG test results of these five blood donors were all reactive, whereas the nucleic acid test results were negative. Neutralizing antibody was detected in 440 of 444 blood samples, with a reactive rate of 99.10%, and 71.59% of the reactive donors had a neutralizing antibody level of 10 μg/mL or more. 【Conclusion】 Blood donors in Guangzhou have a high level of SARS-CoV-2 antibody, which is sufficient to provide convalescent plasma for clinical treatment.

【Objective】 HLA-DRB1 * 11:01, as a class HLA-Ⅱ gene, was reported to be associated with spontaneous clearance of HCV in Han and Li population. Our study was to investigate the effects of viral selection pressure and CD4+T cell epitope on the natural outcome of HCV infection in HLA-DRB1 * 11:01 positive infected patients. 【Methods】 The positive selection sites and population growth of E1E2 and NS3 genes of common HCV 6a in HLA-DRB1 * 11:01 positive and negative groups in Guangdong were respectively analyzed. The peptide library covering the conserved regions of common HCV genotypes was used to stimulate HCV spontaneous clearance group and chronic infection group using ELISPOT method. Reactive peptides were obtained according to the number of spot-forming cells per well and the frequency of occurrence in different groups. 【Results】 The positive selection sites (PSSs) of E1E2 and NS3 of common HCV 6a in HLA-DRB1 * 11:01 negative group were greater than those in HLA-DRB1 * 11:01 positive group. Furthermore, the number of PPSs in CD4+T cell peptide in HLA-DRB1 * 11:01 negative group were also greater than those in HLA-DRB1 * 11:01 positive group; Both groups of HCV 6a had a population growth in Guangdong, and the expansion trend of HLA-DRB1 * 11:01 negative group was significantly higher than that of HLA-DRB1 * 11 :01 positive group. Compared to HCV chronic infection group, the response rate of HCV spontaneous clearance group to five peptides (C-52 E2691-707, C-119 NS31545-1560, C-134 NS4A1669-1684, C-154 NS4B1912-1927, C-159 NS4B1929-1944) was higher. However, the HCV chronic infection group showed a higher response rate to two of the peptides(C-111 NS31497-1512, C-130 NS31650-1665). When HLA-DRB1 * 11:01 typing was considered, there was no significant difference in HCV-specific immune response generated by PBMCs between HLA-DRB1 * 11:01 positive and HLA-DRB1 * 11:01 negative groups. 【Conclusion】 This study revealed the relationship between viral selection pressure of HLA-DRB1 * 11:01 HCV infected persons and CD4+T cell antigen epitopes. At the same time, CD4+ T cell antigen epitopes of HCV pan-genotype were obtained, providing basic data for the development of T cell vaccine suitable for HCV pan-genotype.

Intestinal ischemia/reperfusion injury (ll/RI) is a common pathological process in clinical practice. Ischemia/reperfusion causes damage to intestinal mucosa and distant organs, and induces systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Autophagy is a defense regulation mechanism under stress conditions, which can maintain the homeostasis of cytoplasm, proteins and organelles. The mechanism of autophagy is complex, which is Intestinal ischemia/reperfusion injury (II/RI) is a common pathological process in clinical practice. Ischemia/reperfusion causes damage to intestinal mucosa and distant organs, and induces systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Autophagy is a defense regulation mechanism under stress conditions, which can maintain the homeostasis of cytoplasm, proteins and organelles. The mechanism of autophagy is complex, which is co-regulated by protein complexes encoded by evolutionarily conserved autophagy-related gene (ATG) and a variety of signaling molecules and pathways. Studies have found that autophagy is involved in the process of intestinal ischemia-reperfusion injury. Therefore, revealing the mechanism of autophagy in II/RI can provide evidence for the prevention and treatment of II/RI.

【Objective】 To study the CD4 T cell epitopes in Core and NS3 protein of genotype 1(GT1) and 6(GT6) of hepatitis C virus(HCV). 【Methods】 A total of 298 overlapping peptides(16-mer) spanning Core and NS3 protein of GT1 and GT6 HCV were synthesized. Peripheral blood mononuclear cells(PBMCs) from 17 HCV+ and 7 healthy blood donors were stimulated by peptide pools, followed by evaluating T cell response by IFN-γ ELISPOT, by which 21 peptides with positive results were found. These peptides were further applied to individually stimulate 20 HCV+ and 18 healthy PBMCs. The differences of responsive frequencies to the 21 positive peptides between the two study groups were compared. 【Results】 Pooled and individual peptide stimulation tests showed that HCV+ PBMCs were responsive to the stimulation of 5 peptides(GT1 NS31273-1288 and NS31315-1330; GT6 NS31033-1048, NS31087-1102 and NS31351-1366), with a responsive frequency ranging 18.9%-27.0%. In contrast, healthy PBMCs were not or low responsive(0%-4.0%) to these five peptides. The responsive frequencies were statistically different between the two groups(P<0.05). No reported epitopes in IEDB were found identical with these 5 peptides via sequence alignment. 【Conclusion】 Our study identified novel CD4 T cell epitopes in NS3 protein of GT1 and GT6 HCV, which has potential application value for the research and development of HCV vaccine.

【Objective】 To learn the situation of the evolution process of HCV virus population and the selection pressure of HCV NS5B in intravenous drug users (IDUs) in Guangdong. 【Methods】 141 blood samples from hepatitis C virus (HCV) RNA-positive blood donors and 58 from HCV patients in Guangdong were randomly collected for HCV NS5B sequence amplification, combined with HCV NS5B sequences from blood donors and IDUs obtained by sequencing previously(between 2009 and 2011). Homology analysis was performed by Molecular Evolutionary Genetics Analysis (MEGA) software, evolutionary analysis were performed by Bayesian Evolutionary Analysis Sampling Trees (BEAST) software package. Selection pressure analysis was performed on sequences isolated from IDUs by Datamonkey online software package with Mixed Effects Model Evolution (MEME) method, and the population expansion of species were analyzed using Tajima and Fu neutrality test by Arlequin software. 【Results】 The comparison results of internal homology among different subtypes of IDUs in this group were as follows : HCV-3b had the highest homology (97%), followed by HCV-3a (96%), HCV-6a (95%) and HCV-1b (94%); HCV evolution rate analysis showed that HCV-1b had the fastest evolution rate [2.17E-03 substitutions/site/year (y/y/y)], followed by HCV-3b (2.12E-0 y/y/y), HCV-3a (1.58E-03 y/y/y) and HCV-6a (1.28E-03 y/y/y). The analysis on effective population of HCV: 1980~1990 was rapid growth period for HCV-6a, 1990~1995 period for HCV-1b, and 2000~2007 period for HCV-3a. HCV population genetic characteristics was as follows: HCV-1b, 3a, 3b and 6a experienced population expansion, among which 3a and 3b were the most obvious. As to the analysis of HCV selection pressure, two positive selection sites (235 and 243)were found in the 339 nucleotide fragment of the NS5B sequence in injecting drug users, but mutation only occurred at position 316 [mutation rate 1.24% (14/1 130)] among 5 direct antiviral drug (DAA) sites in this gene. 【Conclusion】 The evolution of HCV-3b in Guangdong has showed an obvious trend of population expansion, with a high proportion and homology especially in the local IDUs. HCV-3b should be the focus of HCV prevention and control in this region. Given that the positively selected sites of the HCV NS5B gene region of IDUs in Guangdong are non-DAA binding sites, DAA is expected to demonstrate a good effect on these patients.