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 observe and analyze the surface electromyography activity of quadriceps femoris of knee osteoar-thritis(KOA)patients. Method:The surface electromyography of vastus lateralis,rectus femoris,and vastus medialis were recorded and analyzed in 30 KOA patients and 30 normal people during isokinetic knee flexion or extension at veloci-ties of 60 °/s,90 °/s or 180 °/s.We also record clinical indicators(muscle thickness and degree of knee pain)of the KOA group and evaluate the correlation between electromyographic data and clinical indicators. Result:Compared with the healthy control group,the KOA group had significantly lower knee extensor mo-ment during isokinetic knee flexion or extension at velocities of 60°/s(P＜0.001),90°/s(P＜0.01),or 180°/s(P＜0.01).Statistics showed that there were significant differences in the median frequency difference rate of vastus lateralis(P＜0.05)and root mean square value of rectus femoris(P＜0.01)between the healthy control group and the KOA group under 60°/s angular velocities.There was a significant difference in the root mean square value of rectus femoris(P＜0.05)between the two groups at velocities of 90°/s.Statistics revealed that the median frequency difference rate(P＜0.05)and root mean square value(P＜0.05)of rectus femoris had changed significantly at the velocities of 180°/s.The results of both multiple regression and random forest algo-rithm showed that knee extensor moment was the strongest predictor between electromyographic characteristics and clinical indicators. Conclusion:The strength of quadriceps femoris in KOA patients was decreased.Thus,the patient may need more muscles to complete the same action,which was easy to cause muscle fatigue.The knee extensor moment was closely related to the quadriceps femoris thickness and the degree of knee pain.It offers important advantag-es for the diagnosis and assessing the severity,which may provide the way for the future study of KOA.

【Objective】 To explore the effectiveness of using donor plasma reinfusion to flush the leukoreduction system (LRS) chamber during the final reinfusion phase with the Trima Accel automated blood collection system in preventing the reduction of CD4+ and CD8+ T lymphocytes. 【Methods】 A longitudinal and cross-sectional study was designed. CD4+ count<200 cells/μL and CD8+ count<125 cells/μL were considered as the criteria for deficiency. Eighteen first-time platelet donors were followed up. The lymphocyte count was measured at 0, 3-6 and 7-14 times of blood donation in the last 300 days. 170 healthy blood donors who have not donated blood were selected as the control group. According to the cut-off point(October 2021), 88 blood donors who mainly used automatic blood collection system to donate platelet apheresis in the last 365 days(median blood donation times ≥17.5)were divided into three groups(A, B and C)and blood samples were obtained. The time for Groups A, B and C started donating platelet apheresis were as follows: Group A: before October 2019, Group B: from October 2019 to September 2021, Group C: after October 2021. Blood samples were analyzed to obtain blood counts including CD4 + and CD8 + T lymphocytes. Blood samples were analyzed to obtain blood cell counts including CD4+ and CD8+ T lymphocytes. Through a comparative analysis, this study aimed to determine if there are any statistical differences in the detection indices between the follow-up groups with varying frequencies of blood donation, the control group, and groups A, B, and C. This approach was employed to infer the efficacy of donor plasma reinfusion in flushing the leukoreduction system (LRS) chamber for preventing the decline of CD4+ and CD8+ T lymphocytes. 【Results】 Eighteen first-time blood donors who were converted to regular platelet apheresis donors did not show a decrease of CD4 + and CD8 + T lymphocytes in the 5 th and 11 th blood donation (median number of blood donation), and there was no significant difference between the above indexes and those in the 0 th blood donation. Among the previous frequent blood donors, the CD4+ and CD8+ T lymphocyte counts in Group B and Group C are both higher than the standard value, showing no statistical difference from the control group. Among regular blood donors, the CD4+ and CD8+ T lymphocyte counts in groups B and C were higher than the criteria values, and had no statistical difference compared to the control group.The CD4+ T lymphocyte count in Group A was normal, with only one donor in Group A having a CD8+ T lymphocyte count below 125 cells/μL. This donor has donated 281 times of platelet apheresis, and the group he belongs to has started blood donation 2-21 years(median of 5 years) before the adjustment of reinfusion mode. The CD4+ and CD8+ T lymphocyte counts in Group A showed significant differences compared to the control group, with median counts (Group A/Control Group) of 359/521 and 257/372, respectively, P<0.001. In Group A, 0%(0/35) had a CD4+ count below 200 cells/μL, and 2.85%(1/35) of donors had a CD8+ count below 125 cells/μL, which was far lower than the proportion of CD4+ and CD8+ T cell deficiency found in regular apheresis donors by John M. Gansner and Mahboubeh Rahmani. The study showed that the adjustment of the plasma reinfusion mode did not further reduce the T lymphocyte counts in blood donors, but instead further restored the T lymphocyte counts in regular blood donors. This indicated that after the adjustment of plasma reinfusion mode, blood donors might not have lost CD4+ and CD8+ T lymphocytes during blood donation, or only lost a small amount, and can recover even if they donate platelet apheresis frequently. 【Conclusion】 Trima Accel automated blood collection system has a good effect on preventing CD4 + and CD8 + T lymphocytes from being reduced by flushing the LRS chamber with donor plasma.

Objective To explore the regional differences in nursing human resource allocation and the dynamic evolution in the western region,in order to provide a scientific and effective basis for the balanced allocation of nursing human resources.Methods Dagum's Gini coefficient,kernel density estimation method and Markov chain were employed to analyze the regional differences,dynamic evolution and trend prediction of nursing human resource allocation in 12 provinces(autonomous regions and municipalities)in western China from 2011 to 2020.Results From the point of view of regional differences,the overall regional differences in the allocation of nursing human resources are on a downward trend and stem mainly from intra-regional differences;the overall regional differences between urban and rural areas stem mainly from inter-regional differences.From the perspective of dynamic evolution,nursing human resources have been continuously upgraded and the absolute difference in the allocation level has gradually increased.From the perspective of trend prediction,the transferring probability between different types of nursing human resource allocation in the west is low,and spatial factors have a polarizing effect on it.Conclusion The level of nursing human resources allocation in the western region has gradually increased,and the overall development goes towards the level of equalization,and the level of nursing human resources allocation in each type is stable and significantly affected by spatial factors.The government should establish regional,urban,and county nursing specialty alliances as well as innovative information-based nursing service models,and implement nursing talent training mechanisms to improve the balanced allocation of nursing human resources in the western region.

AIM: To investigate the effect of dapagliflozin on myocardial injury in type 1 diabetes mice and its mechanism. METHODS: Normal C57BL / 6J male mice were randomly divided into normal control group (Control), diabetes cardiomyopathy group (DCM) and dapagliflozin group (DAPA). The model of diabetes was induced by streptozotocin (STZ) and given maintenance feed. DAPA group was given 10 mg · kg

Guided bone regeneration technology applied in alveolar bone defect regeneration is based on the barrier function and space maintenance of the barrier membrane. Therefore, traditional development strategies for barrier membranes focus on their physical barrier function, degradation characteristics and biocompatibility to avoid immunogenicity. However, not only does the barrier membrane passively block connective tissue, it is recognized as a “foreign body”that triggers a persistent host immune response, known as a foreign body reaction. The theories of osteoimmunology reveal a close relationship between the immune system and bone system and emphasize the role of immune cells in bone tissue-related pathophysiological processes. Based on these findings, we propose a novel development strategy for barrier membranes based on immune microenvironment regulation: by manipulating mechanical properties, surface properties and physiochemical properties, barrier membranes are endowed with an improved immunomodulation ability, which helps to regulate immune cell reactions to induce a favorable local immune microenvironment, thus coordinating osteogenesis and osteoclastogenesis as well as barrier membrane degradation to increase the efficiency of barrier membranes in GBR applications. In this paper, we review the development of barrier membranes and their close relationship to the immune microenvironment concerning bone regeneration and membrane degradation. Additionally, the outcomes of research on barrier membranes based on the regulation of the immune microenvironment have been summarized to improve the osteogenesis efficiency of barrier membranes and solve the problem of the regeneration and repair of bone defects, especially alveolar bone defects.

Objective:To evaluate the safety and efficacy of 27G micro-incision vitrectomy surgery (MIVS) combined with intravitreal injection of ranibizumab (IVR) in the treatment of retinopathy of prematurity (ROP) with early intervention failure.Methods:Retrospective case series was performed. Fourteen eyes (11 infants) with ROP who underwent 27G MIVS combined with IVR were included from March 2016 to January 2018 in Shenzhen Eye Hospital. Among them, there were 5 males with 7 eyes, 6 females with 7 eyes. The average gestational age of the infants was 28.12±0.90 weeks; the average birth weight was 1 023.64±200.96 g. Before the early clinical intervention, 1 infant (2 eyes) had ROP in zone Ⅰ stage 3 with plus disease, 8 infants (10 eyes) had ROP in zone Ⅱ stage 3 with plus disease, and 2 infants had ROP in aggressive posterior ROP. Six eyes underwent laser photocoagulation, while 8 eyes received laser therapy combined with IVR. Six eyes of stage 4A ROP and 8 eyes in stage 4B. Retinal detachment was detected with a mean of 10.44±9.21 weeks. At the time of surgery, the average post-conceptional age was 48.02±8.09 weeks. All the affected eyes were treated with standard sclera with three incisions 27G MIVS. During the operation, only local vitrectomy was performed to release and clear fibroascular proliferation in the optic disc, anterior macular area and pericristal area. After surgery, 10 mg/ml of ranibizumab 0.03 ml was injected into the vitreous cavity. The average follow-up time was 23.36±8.34 months. The primary objectives were the condition of retinal reset, ROP progression control and complications.Results:All patients had uneventful surgeries with an average duration of 32.86±9.35 mins. Of the 14 eyes, 12 eyes (85.71%) were controlled, 8 eyes (57.14%) had a good rearrangement of macular structure, while 4 eyes with macular traction. Two eyes had ROP progression, recurrence of retinal detachment, posterior synechia. Complicated cataract was in 1 eye. Proliferative vitreoretinopathy and retinal detachment was in 1 eye after 7 months the operation.Conclusion:27G MIVS combined with IVR is a safe and effective treatment for ROP with early clinical intervention failure.

Objective:To explore the clinical application values of a nomogram based on preoperative breast MRI and axillary ultrasonography imaging parameters for predicting the risk of sentinel lymph node (SLN) metastasis in early-stage breast cancer patients.Methods:Three hundred and ninty-seven female patients (mean age 48.0±10.7 years old, range 25-81 years old) who admitted to Sun Yat-sen University Cancer Center from May 2007 to December 2017 were enrolled in this study. All patients were diagnosed as primary unilateral invasive early-stage breast cancer confirmed by surgical pathology. Preoperative breast MRI, axillary ultrasonography and clinical pathological data of enrolled patients were retrospectively analyzed. According to the pathological results of sentinel lymph node biopsy (SLNB), the cases were divided into negative SLN group ( n=200) and positive SLN group ( n=197). Clinicopathologic data, MRI and axillary ultrasound features were analyzed and compared between two groups. Logistic regression analysis was used to select independent risk factors. Then a predictive model was constructed and a nomogram was made for visualizing the associations between the predictive factors and SLN metastasis. Goodness-of-fit of the model was evaluated by using the Hosmer-Lemeshow test. Predictive performance was assessed based on the receiver operating characteristic (ROC) curves. Bootstrap resampling was performed for internal validation. Results:Significant differences were found in patient age, lymphovascular invasion status, PR status, HER2 status and molecular subtype between negative and positive SLN groups (all P<0.05); MRI features including tumor size, mass margin, long and short diameter, as well as the ratio of long to short diameter of LNs, LN margin, presence or absence of LN hilum, and axillary LNs symmetry were found significantly different between negative and positive SLN groups (all P<0.05); as for the axillary LN ultrasonography parameters, the interface between cortex and medulla, presence or absence of cortical thickening, and LN hilum were significantly different between negative and positive SLN groups (all P<0.05). Logistic regression analysis results showed that several factors could be identified as predictors of SLN metastasis, including patient age, MRI features (lymph node margin, presence or absence of lymph node hilum, and lymph node symmetry), axillary ultrasonography descriptors (presence or absence of cortical thickening) and pathological factors (lympovascular invasion, PR and HER2 status). The nomogram with patient age and the above imaging factors showed good,prediction performance with the area under the ROC as 0.778. Combining with the pathological parameters, the prediction performance of the nomogram model was significantly improved, yielding the area under the ROC of 0.866. Conclusions:The nomogram based on breast MRI and axillary ultrasonography can be applied as a noninvasive quantitative tool to predict the risk of SLN metastasis in early-stage breast cancer, which may facilitate decision-making for axillary treament strategy preoperatively.

Objective:To explore the association between interleukin(IL)-28B single nucleotide polymorphisms and natural outcome of hepatitis C virus.Methods:The IL-28B rs12979860 locus was genotyped in 266 HCV infected volunteer blood donors(107 spontaneous cleared and 159 chronic infection) and 97 healthy controls using Sanger sequencing assay.The difference in rs12979860 genotypes and allele frequencies between the six groups(107 spontaneous cleared and 159 chronic infection,266 HCV infection and 97 healthy controls,159 chronic infection and 97 healthy controls) were analyzed by statistics.Results:159 HCV chronic infection,107 spontaneous cleared and 97 healthy controls,were shown more CC genotype,accounting for 83.6%,95.3%and 86.6%,respectively, while the CT genotype accounted for 16.4%,4.7%and 13.4%respectively.No TT genotype was found.The CC/CT genotype was not significant difference between HCV infection and healthy controls,chronic infection and healthy controls(χ2=0.204,P=0.652;χ2=0.406,P=0.524),but between chronic infections and spontaneous clearance had statistically significant(χ2=8.474,P=0.004),the frequence of C allele in spontaneous cleared was higher than HCV chronic infection(χ2=7.949,P=0.005).Conclusion: The gene polymorphism of IL-28B rs12979860 is not related to HCV susceptibility,but there are differences in chronic infection and spontaneous cleared,showing the C allelic in favor of HCV spontaneous cleaed.