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.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Objective To introduce a modified technique of right ventricular outflow tract (RVOT) reconstruction using a handmade bicuspid pulmonary valve crafted from expanded polytetrafluoroethylene (ePTFE) and to summarize the early single-center experience. Methods Patients with complex congenital heart diseases (CHD) who underwent RVOT reconstruction with a handmade ePTFE bicuspid pulmonary valve due to pulmonary regurgitation at Guangdong Provincial People’s Hospital from April 2021 to February 2022 were selected. Postoperative artificial valve function and right heart function indicators were evaluated. Results A total of 17 patients were included, comprising 10 males and 7 females, with a mean age of (18.18±12.14) years and a mean body weight of (40.94±19.45) kg. Sixteen patients underwent reconstruction with a handmade valved conduit, with conduit sizes ranging from 18 to 24 mm. No patients required mechanical circulatory support, and no in-hospital deaths occurred. During a mean follow-up period of 12.89 months, only one patient developed valve dysfunction, and no related complications or adverse events were observed. The degree of pulmonary regurgitation was significantly improved post-RVOT reconstruction and during follow-up compared to preoperative levels (P<0.001). Postoperative right atrial diameter, right ventricular diameter, and tricuspid regurgitation area were all significantly reduced compared to preoperative values (P<0.05). Conclusion The use of a 0.1 mm ePTFE handmade bicuspid pulmonary valve for RVOT reconstruction in complex CHD is a feasible, effective, and safe technique.

Objective:To investigate the effect of circulating plasma cell(CPC)on the prognosis of multiple myeloma(MM),and to es-tablish and validate a modified CPC-RISS staging system based on CPC and RISS.Methods:A retrospective analysis was performed for the clinical data of 639 treatment-na?ve patients with MM who were treated in Department of Hematology,Xijing Hospital,from January 2006 to June 2023.Peripheral blood smear was used to calculate the percentage of CPC in patients,and the impact of CPC and other related factors on the prognosis of MM patients was analyzed.A CPC-RISS staging system was established based on RISS stage and the percentage of CPC,and the differences in survival and prognosis were analyzed between patients with different stages.Results:Compared with the patients without CPC,detectable CPC was significantly associated with various high-risk factors for MM,and the MM patients with CPC had a lower complete remission rate and shorter overall survival time and progression-free survival time.The modified CPC-RISS staging system was used to classify the patients with MM into four stages,and there were significant differences in median survival time and progression-free survival time between the patients with different stages of MM.Conclusion:The MM pa-tients with the presence of CPC exhibit more aggressive features,worse response to treatment,and a reduction in long-term survival rate.The modified CPC-RISS staging system can effectively predict the prognosis of treatment-na?ve MM patients.

Objective To evaluate the influencing factors of aspiration in neurological critically ill patients by Meta-analysis.Methods PubMed,Embase,Web of Science,CNKI,and Wanfang Data were searched from inception to 1 October,2023,to obtain relevant studies on influencing fac-tors of aspiration in neurological critically ill patients.The literature screening,data extraction and quality evaluation were completed by two researchers.RevMan 5.4 and Stata 13.0 software were ap-plied for pooled Meta-analysisand assessed publication bias,respectively.Results A total of 8 arti-cles,including 1,315 neurocritical care patients,were included in this study.Nine influencing factors related to aspiration were extracted for Meta-analysis.The Meta-analysis results showed that the three influencing factors that caused aspiration in neurocritical care patients were stroke history(OR=5.03,95％CI,2.71 to 9.32,P＜0.000 01),National Institutes of Health Stroke Scale(NIHSS)score＞10(OR=3.35,95％CI,1.75 to 6.42,P=0.000 3),and gastric residual volume＞150mL(OR=7.13,95％CI,2.55 to 9.96,P=0.001).Conclusion This study provides a scientific basis for clinical healthcare professionals to early identify high-risk patients for aspiration,take targeted inter-vention measures,and prevent the occurrence of aspiration.

Objective:To explore the material basis and potential mechanism of Sanhuang Yishen Capsules in the treatment of diabetes through network pharmacology, molecular docking and experimental verification.Methods:The active components and targets of Sanhuang Yishhen Capsules were screened using China Natural product chemical composition database and SymMap database, and the related targets of T2DM were screened by GeneCards database. The "Chinese materia medica-active component-target" network was constructed, and the intersection genes were enriched by GO and KEGG using R language. Key active components were selected for molecular docking verification with potential core targets. 60 rats were divided into normal group, model group, and Sanhuang Yishen Capsules group according to random number table method, with 15 rats in each group. In addition to the normal group, the diabetic rat model was prepared in the other groups, and the corresponding drugs were intragastric in each group for 8 weeks. The levels of fasting blood glucose (FBG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) were measured by radioimmunoassay. Western blotting was used to detect protein expressions of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF), Akt serine/threonine kinase 1 (AKT1), recombinant tumor protein p53 (TP53), and recombinant caspase 3 (CASP3).Results:A total of 160 active components and 298 targets of Sanhuang Yishen Capsules, 2194 targets related to T2DM, and 166 intersection targets were obtained. GO and KEGG analyzed a series of biological reaction processes mainly involved in signal transduction, oxidative stress, apoptosis, etc., and mainly involved in the regulation of P13K/Akt, P53, CASP3 and other targets. The results of molecular docking showed that the main active components obtained by screening had strong binding with the target. Compared with model group, FBG, FINS, HOMA-IR, TP53 and CASP3 in Sanhuang Yishen Capsules group decreased ( P<0.05), EGFR, EGF and Akt1 proteins increased ( P<0.05). Conclusion:The mechanism of Sanhuang Yishen Capsules for the treatment of may be related to the regulation of EGF/EGFR/P13K/Akt signaling pathway, TP53 signaling pathway, CASP3 signaling pathway, PPARG signaling pathway, ESR1 signaling pathway, PTGS2 signaling pathway, CAT signaling pathway and CTNNB1 signaling pathway.

Objective To construct and validate a risk prediction model for enteral nutrition feeding intolerance (FI) in patients with severe cerebral hemorrhage based on machine learning algorithms. Methods The clinical data of 485 patients with cerebral hemorrhage admitted to the neurological intensive care unit of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from January 2020 to December 2022 were retrospectively analyzed. The patients were randomly divided into training set (n=339) and validation set (n=146) in a 7 to 3 ratio. Five machine learning algorithms were used to construct FI risk prediction models. The receiver operating characteristic (ROC) curve was plotted, and the model with the best predictive performance was selected based on the area under the curve (AUC). A nomogram model was constructed based on the optimal model. The calibration curve and decision curve analysis (DCA) were used to evaluate the calibration and clinical net benefit of the nomogram model. Results The incidence of enteral nutrition FI in patients with severe cerebral hemorrhage was 38.4%(186/485). Among the five machine learning algorithm models, the Logistic regression model had the best predictive performance(AUC=0.88). The analysis results of the Logistic regression model showed that the use of diuretics, mechanical ventilation, Glasgow Coma Scale score ≤5, vasoactive drugs, and albumin level<35 g/L were risk factors for enteral nutrition FI in patients with severe cerebral hemorrhage. A nomogram model was further constructed based on these five risk factors. The calibration curve analysis showed that the calibration curve fitted well with the ideal curve, indicating a high calibration degree of the nomogram model. The DCA results showed that when the threshold probability was 5% to 73%, the application of the nomogram model for screening could clinically benefit patients. Conclusion The construction of a nomogram model for predicting the risk of enteral nutrition FI in patients with severe cerebral hemorrhage based on machine learning methods can help to early screen high-risk patients for enteral nutrition FI and timely formulate preventive measures, thereby reducing the incidence of enteral nutrition FI in patients with severe cerebral hemorrhage.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Objective: To investigate the level of maternal and infant health literacy and its influencing factors among lying-in women, so as to provide insights into formulating maternal and infant health education and promotion strategies. Methods: Lying-in women were sampled from Children's Hospital of Shanxi using a cluster sampling method from March to September 2022. Demographic characteristics, maternal and infant health literacy, and health education demands were collected through a questionnaire survey. Factors affecting maternal and infant health literacy among lying-in women were identified using a multivariable logistic regression model. Results: A total of 1 099 questionnaires were allocated, and 1 059 valid questionnaires were recovered, with an effective rate of 96.36%. Participants had a mean age of (30.93±4.01) years, 930 urban residents (87.82%), and 706 pluripara (66.67%). The overall prevalence of maternal and infant health literacy was 35.51% among lying-in women, and the prevalence rates of basic knowledge and concept, healthy lifestyles and behaviors and basic skills were 47.69%, 83.10% and 38.81%, respectively. Multivariable logistic regression analysis showed that educational level (diploma or undergraduate degree, OR=3.916, 95%CI: 1.250-9.031; master degree and above, OR=4.557, 95%CI: 1.498-11.460), occupation (company employees, OR=2.701, 95%CI: 1.385-5.268; medical staff, OR=2.981, 95%CI: 1.289-6.893), pluripara (OR=5.649, 95%CI: 3.919-8.142), participating in health education activities (OR=2.332, 95%CI: 1.524-3.570), and participating in schools for pregnant women (OR=2.252, 95%CI: 1.541-3.291) were promoting factors for maternal and infant health literacy; while gestational hypertension (OR=0.255, 95%CI: 0.133-0.488) and gestational diabetes (OR=0.318, 95%CI: 0.211-0.478) were inhibiting factors for maternal and infant health literacy. Most participants acquired health knowledge through online media (62.42%), and hoped to participate in health education activities through online media publicity (68.18%). Conclusions The maternal and infant health literacy level of lying-in women in this survey is associated with education, occupation, parturition frequency, participation in health education activities, participation in schools for pregnant women, gestational hypertension and gestational diabetes.