ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

As the need for antibody production rises, there is an urgent need to lower the costs and enhance the efficiency of the separation process. Currently, the chromatographic media used for antibody separation and purification often focus on individual properties of antibodies, such as affinity, hydrophobicity, and charge, leading to issues like low purification efficiency or inadequate adsorption capacity. To address this, an electrostatically coupled polypeptide affinity medium (FD7-3, 5-diaminobenzoic acid n-sepharose, FD7-DA-Sepharose) was developed for rapid purification of antibodies from cell culture supernatant. This medium utilized 3, 5-diaminobenzoic acid as a spacer to attach the heptapeptide-affinity ligand (FYEILHD, FD7) to agarose microspheres. Antibodies could be adsorbed through charge interactions with the carboxyl functional group of the FD7-DA-Sepharose spacer, while FD7 enhanced electrostatic coupling and affinity adsorption through synergistic effects, significantly increasing the adsorption capacity while maintaining the affinity and specificity. The influences of pH and ionic strength on adsorption capacity were investigated with human immunoglobulin as a model protein. The static adsorption capacity (Q_m) of FD7-DA-Sepharose in the solution of pH 6.0 reached 67.73 mg/mL, representing a 52.68% increase compared with that (44.36 mg/mL) of the commercial Protein A affinity medium. Furthermore, the elution conditions for FD7-DA- Sepharose were mild (20 mmol/L PB, 0.5 mol/L NaCl, pH 6.0), in contrast to the harsh acidic elution (pH 2.7-3.6) typically associated with Protein A, which can damage antibody integrity. The FD7-DA-Sepharose medium was then employed to purify antibodies from cell culture supernatant, achieving the yield of 94.8% and the purity of 98.4%. The secondary structure of the purified antibody was determined by circular dichroism spectroscopy. The results demonstrated that FD7-DA-Sepharose enabled efficient purification of antibodies from cell culture supernatant, which provided a cost-effective solution (approximately one-third the price of commercial Protein A affinity medium) with gentle elution conditions that preserve the natural conformation of antibodies. This approach paves a novel, economical, and efficient way for the separation and purification of antibodies from cell culture supernatant.
Chromatography, Affinity/methods* ; Static Electricity ; Humans ; Sepharose/analogs & derivatives* ; Peptides/chemistry* ; Adsorption ; Antibodies/isolation & purification*

Objective:To investigate the efficacy of Naikan cognitive therapy(NCT)combined with medica-tion in improving depressive symptoms and sleep quality in patients with chronic schizophrenia.Methods:Patients were included if they met the following criteria:diagnosed with schizophrenia based on ICD-10 criteria,a disease course of ≥2 years,stable condition under maintenance antipsychotic medication,presence of depressive symptoms and sleep quality issues,and no use of antidepressants in the past two months.A total of 64 eligible patients were randomly assigned to the NCT group(n=32)or the mental health education(MEC)group(n=32).The interven-tion lasted 6 days,with 2 patients from each group dropping out.The Beck Depression Inventory-Ⅱ(BDI-Ⅱ)and Pittsburgh Sleep Quality Index(PSQI)were used to assess depressive symptoms and sleep quality.Results:After the intervention,the BDI-Ⅱ score difference(post-treatment score minus pre-treatment score)in the NCT group was significantly lower than that in the MEC group(P＜0.001).Similarly,the PSQI total score difference was also lower in the NCT group compared to the MEC group(P＜0.001).Conclusion:Adding Naikan cognitive therapy to routine medication treatment can effectively improve depressive symptoms and sleep quality in patients with chronic schizophrenia.

Objective:To observe the stability of vertical dimension of occlusion (VDO) and mandibular position in full-mouth occlusal reconstruction subjects by means of digital occlusal analysis.Methods:Six subjects who had completed full-mouth occlusal reconstruction by intraoral functional generated path technique for more than three years in the Department of Prosthodontics, Peking University School and Hospital of Stomatology were enrolled for follow-up observation, all six patients were male, with an age of (53.6±8.4) years. The digital dentition model and occlusal contact at baseline and three years follow-up review after restoration were recorded by intraoral laser scanning, and the changes in occlusal surface morphology, occlusal contact area and mandibular position (mandibular overall deviation and mandibular reference plane average angle deviation) were measured in reverse engineering software. The Wilcoxon signed rank test was used to statistically analyze the changes of horizontal and vertical overbite of anterior teeth and VDO of posterior teeth between baseline and three years follow-up after reconstruction.Results:The prosthesis in the 6 subjects were intact at the time of follow-up, and there was no significant change in occlusal morphology compared with that at the baseline right after restoration delivery, and the occlusal contact in maximum intercuspid position was stable. The overall deviation of the lower jaw was (0.19±0.06) mm, and the angular deviation of the mandibular reference plane was 0.72°±0.38°. The chromatic scale of occlusal contact showed that the occlusal contact in some areas was heavier during the three years post-delivery, and the overbite of anterior teeth and the VDO of posterior teeth showed no statistical difference compared with that in the baseline (all P>0.05). Conclusions:This study suggests that the occlusal contact distribution and jaw position relationship can be maintained after 3 years of full-mouth occlusal reconstruction, and there is no significant change in the anterior overbite and VDO.

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.

As people age, older adults experience problems such as aging and degeneration of systemic organs and skin barrier function, leading to a high incidence of dry skin and pressure injuries. Dry skin and pressure injuries interact with each other to exacerbate the failure of skin function, which not only increases suffering, mortality risk, and medical costs for the elderly but also places a heavy burden on society and families. This paper summarizes the epidemiological characteristics of dry skin in the elderly and its influencing factors, the impact of dry skin in the elderly on pressure injuries, and puts forward the prevention and control strategies of "external treatment" and "internal nourishment" to provide a reference for the development of prevention and control strategies for dry skin and pressure injuries in the elderly in China.

Objective:To test the difficulty, discrimination, and reliability of the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire.Methods:Two researchers independently translated the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire and cross-checked it to form a Chinese version of the questionnaire. The Chinese version of the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire consists of 24 items, with correct answers scoring one point and incorrect answers scoring zero points, with a total score of 24 points. Convenience sampling was used to select ICU nurses from 14 GradeⅢ Class A hospitals in five provinces/autonomous regions and two municipalities in China for the survey between April and July 2023. The difficulty index, discrimination index, and Cronbach's α coefficient of the questionnaire were analyzed.Results:A total of 1 121 questionnaires were distributed, with 1 020 valid responses, yielding a valid response rate of 90.99%. The mean score of the 1 020 ICU nurses on the Chinese version of the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire was (16.10±5.58) , with a minimum score of 4.00 and a maximum score of 24.00. The Cronbach's α coefficient of the Chinese version of the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire was 0.91. The questionnaire's overall difficulty and discrimination indexes were 0.67 and 0.59, respectively.Conclusions:The Chinese version of the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire has appropriate difficulty, moderate discrimination, and strong reliability, making it a valuable tool for assessing ICU nurses' knowledge of pressure injury-related topics.

Objective:To summarize the best evidence for oral nutrition management of patients with inflammatory bowel disease (IBD) and to evaluate its effectiveness.Methods:From May 2023 to March 2024, IBD patients, the medical and nursing staff in the Department of Proctology, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, were selected as study subjects using convenience sampling method. Evidence-based nursing was used to summarize the best evidence for oral nutrition management of IBD patients, formulate review indicators, develop best evidence-based practice programs for clinical application through status review and barrier factor analysis. Effectiveness was evaluated at the system level, medical and nursing staff level, and patient level.Results:After evidence-based practice, a multidisciplinary management team and management system for oral nutrition was established at the system level. At the medical and nursing staff level, the oral nutrition knowledge score increased from [50.00 (40.00, 60.00) ] to [100.00 (85.00, 100.00) ], with a statistically significant difference ( P<0.01), and the implementation rate of the three review indicators improved from 0 to 100.00%. At the patient level, oral nutrition knowledge and attitude scores improved from [10.00 (8.00, 12.00) ] and [35.00 (31.00, 40.00) ] to [16.00 (16.00, 16.00) ] and [48.00 (45.00, 48.00) ], respectively, with statistically significant differences ( P<0.01), and the implementation rate of each of the review indicators rose above 80.00% except for indicator 6. The patients' nutrition indicators, including body mass index, waist circumference, left upper arm midpoint circumference and left hand grip strength were improved, and the difference was statistically significant ( P<0.05) . Conclusions:The implementation of evidence-based practice programs can improve the standardization of clinical work of healthcare professionals, enhance patients' nutrition knowledge and attitude, and promote their rational dietary behaviors, thus improving their nutrition status and quality of life.

Objectives:To explore the predictive value of angiography-derived index of microcirculatory resistance(Angio-IMR)for early prognosis in patients with acute ST-segment elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI).Methods:This multicenter study enrolled 1 629 consecutive STEMI patients who underwent successful PCI at three grade A tertiary hospitals(The Second Affiliated Hospital,Zhejiang University School of Medicine;Shengjing Hospital of China Medical University;Renji Hospital,Shanghai Jiao Tong University School of Medicine)from June 1,2017,to May 31,2020.According to postoperative Angio-IMR,patients was stratified into two groups:the Angio-IMR>40 group(n=508)and the Angio-IMR≤40 group(n=1 121).The incidence of major adverse cardiovascular events(MACE;defined as a composite endpoint including cardiac death,heart failure rehospitalization,cardiogenic shock,malignant arrhythmia,cardiopulmonary resuscitation and stent thrombosis)within 1-month post-PCI was compared between the two groups.Results:The median Angio-IMR after PCI was 32.4(22.3,42.6).The cumulative incidence of early-term MACE was significantly higher in patients with Angio-IMR>40,compared to those with Angio-IMR≤40(5.5%vs.2.3%,log-rank P<0.001).Multivariate Cox regression analysis showed that Angio-IMR>40 was an independent predictor of early-term MACE(HR=2.07,95%CI:1.20-3.58,P=0.009).The addition of Angio-IMR enhanced the predicting performance of the clinical risk model to predict early adverse outcomes(AUC:0.820 vs.0.794,P=0.043).Conclusions:In patients with STEMI after PCI,Angio-IMR can predict the occurrence of early-term MACE.The incorporation of Angio-IMR to clinical models significantly improves the model ability to predict early adverse outcomes in these patients.