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.

Objective: To identify core acupoint patterns and elucidate the molecular mechanisms of acupuncture for primary depressive disorder (PDD) through data mining and network analysis. Methods: A comprehensive literature search was conducted across PubMed, Embase, Ovid Technologies (OVID), Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), China National Knowledge Infrastructure Database (VIP), Wanfang Data, and SinoMed Database from database foundation to January 31, 2025, for clinical studies on acupuncture treatment of PDD. Descriptive statistics, high-frequency acupoint analysis, degree and betweenness centrality evaluation, and core acupoint prescription mining identified predominant therapeutic combinations for PDD. Network acupuncture was used to predict therapeutic target for the core acupoint prescription. Subsequent protein-protein interaction (PPI) network and molecular complex detection (MCODE) analyses were conducted to identify the key targets and functional modules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses explored the underlying biological mechanisms of the core acupoint prescription in treating PDD. Results: A total of 57 acupoint prescriptions underwent systematic analysis. The core therapeutic combinations comprised Baihui (GV20), Yintang (GV29), Neiguan (PC6), Hegu (LI4), and Shenmen (HT7). Network acupuncture analysis identified 88 potential therapeutic targets (79 overlapping with PDD), while PPI network analysis revealed central regulatory nodes, including interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, toll-like receptor 4 (TLR4), IL-10, brain-derived neurotrophic factor (BDNF), transforming growth factor (TGF)-β1, C-X-C motif chemokine ligand 10 (CXCL10), mitogen-activated protein kinase 3 (MAPK3), and nitric oxide synthase 1 (NOS1). MCODE-based modular analysis further elucidated three functionally coherent clusters: inflammation-homeostasis (score = 6.571), plasticity-neurotransmission (score = 3.143), and oxidative stress (score = 3.000). GO and KEGG analyses demonstrated significant enrichment of the MAPK, phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and hypoxia-inducible factor (HIF)-1 signaling pathways. These mechanistic insights suggested that the antidepressant effects mediated through mechanisms of neuroinflammatory regulation, neuroplasticity restoration, and immune-oxidative stress homeostasis. Conclusion This study reveals that acupuncture alleviates depression through a multi-level mechanism, primarily involving the neuroinflammation suppression, neuroplasticity enhancement, and oxidative stress regulation. These findings systematically clarify the underlying mechanisms of acupuncture’s antidepressant effects and identify novel therapeutic targets for further mechanistic research.

Objective:To retrieve and evaluate the evidence on the risk grading management of high-risk diabetic foot patients, so as to provide reference for the management of diabetic foot.Methods:According to the "6S" pyramid model of evidence-based resources, evidence on risk grading management of high-risk diabetic foot patients was retrieved in Web of Science, UpToDate, Cochrane Library, PubMed, China National Knowledge Infrastructure, WanFang Data, VIP and other databases, guide websites, and professional association websites. The search period was from the establishment of the database to January 1, 2024.Results:A total of 11 articles were included, including 8 guidelines, one systematic review, one expert consensus, and one expert opinion. There were 24 pieces of best evidence about the risk grading management of high-risk diabetic foot patients, covering 8 aspects of risk assessment, risk grading, health records establishment, screening frequency, health education, foot management, exercise management and referral.Conclusions:The best evidence of risk grading management of high-risk diabetic foot patients summarized can provide reference for clinical nurses to carry out evidence-based practice.

Lactic acid bacteria(LAB)were isolated and cultivated from the intestinal contents of rabbits by MRS-CaCO3 solid medium.Identification was achieved through morphological observa-tion,Gram staining,physiological and biochemical characterisation,16S rDNA sequence analysis,and ERIC-PCR analysis.Strains displaying typical Lactobacilli characteristics were exanimated for their biological characteristics,resistance properties,adherence capacity in vitro,colonization abili-ty in vivo,and safety profile.In this study,a total of four strains of Lactobacillus reuteri were iso-lated from rabbits,all of which exhibited typical biological characteristics of LAB.These strains demonstrated inhibitory effects on common pathogenic bacteria in the gastrointestinal tract,with the primary inhibitory substance being bacteriocin.Furthermore,they showed sensitivity to chlor-amphenicol,rifampicin,and erythromycin,and displayed a degree of tolerance to gastrointestinal conditions and high temperature.These stains were capable of successful colonization in rabbits with a higher degree of safety.This study lays a foundation for the development of LAB prepara-tions for the prevention and treatment of rabbit intestinal diseases.

Stevens-Johnson syndrome (SJS), also known as the multifactorial erythematous drug eruption, is a class of adverse reactions of the skin and mucous membranes primarily caused by drug allergy often involving the oral cavity, eyes, and external genital mucosa, generally accompanied by fever, and can be life-threatening in severe cases. In February 2022, the Department of Stomatology, the First Affiliated Hospital of Zhengzhou University admitted a patient with huge inflammatory hyperplasia of bilateral lingual margins secondary to SJS. Upon admission, no other obvious symptoms were observed except for tongue hyperplasia. The patient suffered from a severe adverse drug reaction caused by acetaminophen 2 months ago and was complicated by liver dysfunction and pulmonary infection. After 1 month of treatment and rehabilitation, he developed a secondary tongue mass and was subsequently admitted to Dept. of Oral and Maxillofacial Surgery Ward 2, the First Affiliated Hospital of Zhengzhou University. After completing the examination, the tongue mass was surgically removed. After a follow-up of 11 months, the patient's condition was satisfactory and no temporary discomfort was observed. The case of tongue mass secondary to SJS is extremely rare. If a stomatologist encounters a similar case, we should carefully inquire about the drug allergy history and recent medication history, and be alert to whether or not they had adverse drug reactions recently.
Male ; Humans ; Stevens-Johnson Syndrome/drug therapy* ; Hyperplasia/pathology* ; Skin ; Drug Hypersensitivity/pathology* ; Tongue

OBJECTIVE： To study the effects of Atractylodes macrocephala ethanol extract （AM） on life span of Caenorhabditis elegans（called N 2 nematode for short ），and to investigate its mechanism based on transcription factor SKN- 1/ nuclear factor E 2 related factor 2（Nrf2）. METHODS ：N2 nematode were divided into blank control group ，positive control group （100 μ mol/L curcumin，similarly hereinafter ），AM low-dose ，medium-dose and high-dose groups （100，200，300 μ g/mL， similarly hereinafter ）. The effects of AM on the life span （by average survival time ）of N 2 nematode under normal condition and oxidant stress condition （40 mmol/L H 2O2）as well as its effects on reproductive capability （by the number of filial generation ）of N2 nematode under normal condition were investigated . 700 μmol/L H2O2 was used to establish neuroblastoma cells N 2a oxidant stress model. Effects of positive control ，low-dose，medium-dose and high-dose of AM on the survival rate of model cells were detected by MTT method. After human embryonic renalepithelial cells 293T were transfected with Nrf 2-ARE plasmid ， the effects of positive control and AM on luciferase activity of Nrf2-ARE were detected by luciferase reporter gene method at low，medium and high dose for 24 h and at medium dose for 12，18 and 24 h. RT-PCR was used to detect the effects ofpositive control ，low-dose，medium-dose and high-dose of AM on the mRNA expression of downstream genes NQO- 1 and HO- 1 of Nrf 2 in N 2a cells as well as mRN A expression of en@hactcm.edu.cn downstream genes GCS- 1，GST-7，GST-10，HSP-60，HSP- 16.2 and SOD- 3 of SKN- 1 in N 2 nematode. RESULTS ：Compared with blank control group ，average survival time of N 2 nematode under normal and oxidant stress condition was significantly prolonged in positive control group and AM groups ；the number of filial generation on the first day （except for AM high-dose group ），the number of filial generation on the second day （except for AM low-dose group ） and the total number of filial generation （except for AM low-dose group ） were increased significantly（P＜0.05 or P＜0.01）. The survival rate of N 2a cells in positive control group ，AM medium-dose and high-dose groups were significantly higher than that of model group （P＜0.05 or P＜0.01）. Compared with blank control group ，Nrf2-ARE luciferase relative activity of 293T cells in positive control group and AM groups as well as Nrf 2-ARE luciferase relative activity of 293T cells in AM medium-dose group after different time of treatment were increased significantly （P＜0.01），in dose-dependent and time-dependent trend. Compared with blank control group ，mRNA relative expression of HO- 1 and NQO- 1（except for positive control group ），GCS-1（except for AM low-dose group ），GST-7（except for positive control group and AM low-dose group ）， GST-10 and HSP- 60（except for AM low-dose group ），HSP-16.2（except for positive control group and AM low-dose group ）and SOD-3 （except for positive control group and AM low-dose group ） were increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：AM can prolong the life span of N 2 nematode under normal and oxidant stress condition and improve the its reproductive capacity ，the mechanism of which may be associated with the activation of SKN- 1/Nrf2 signaling pathway.

Objective: To study the effect of p38 mitogen activated protein kinase (p38 MAPK) on the expression of genes related to enamel development in the enamel epithelium and to provide a basis for the study of the molecular mechanism of enamel development. Methods: The p38 MAPK-specific inhibitor SB203580 dissolved in DMSO was added to the culture medium of mouse mandibular molar tooth germs in vitro as experiment group, and mouse mandibular molar tooth germs treated with the same amount of DMSO were used as control group. Western blot was used to detect the protein expression level of phosphorylated p38 (p-p38) in the enamel epithelium. Real-time PCR was used to detect the mRNA expression levels of runt-related transcription factor 2 (Runx2), osteoblast-specific transcription factor (Osx), ameloblast markers odontogenic ameloblast associated protein (ODAM), amelotin (AMTN), matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4) in the enamel epithelium. Results : Western blot results showed that under the action of the inhibitor SB203580, the phosphorylation level of p38 MAPK in mouse enamel epithelium decreased, and the difference was statistically significant (P < 0.05). Real-time PCR results showed that the expression levels of the transcription factors Runx2 and Osx and the ameloblast markers ODAM, AMTN, MMP20, and KLK4 in the SB203580 group were lower than those in the control group, and the difference was statistically significant (P < 0.05). Conclusion The p38 MAPK signaling pathway can mediate enamel development by regulating the expression of the transcription factors Runx2 and Osx and the ameloblast markers ODAM, AMTN, MMP20 and KLK4 in the mouse enamel epithelium.

PURPOSE: This study aimed to evaluate the racial and ethnic disparities in the incidence of gastric cancer and their temporal trends in the United States. MATERIALS AND METHODS: Using data from 13 cancer registries in the Surveillance, Epidemiology, and End Results database, we assessed such disparities during 1992-2014 in the United States using a variety of disparity metrics. RESULTS: The age-standardized incidence rate of non-cardia gastric cancer was highest in Asian and Pacific Islanders, while the incidence of cardia gastric was highest in non-Hispanic whites in men and was similarly low in all groups in women. The incidence of non-cardia gastric cancer decreased in all groups over time, particularly in Asian and Pacific Islanders (on average by 3% per year). The incidence of cardia gastric remained relatively stable in virtually all racial/ethnic groups. The racial and ethnic disparities in gastric cancer incidence steadily decreased over time as measured on the absolute scale, which was mainly driven by the reduced disparities in non-cardia gastric cancer. The range difference in the incidence of gastric cancer decreased on average by 4.1% per year in men and by 2.6% per year in women from 1992 to 2014. The between group variance decreased by 5.6% per year in men and by 3.4% per year in women. The relative-scale disparity measures generally remained stable over time. CONCLUSION: This study demonstrates decreased racial and ethnic disparities in the incidence of gastric cancer over time in the United States, particularly as measured on the absolute scale.
Asian Continental Ancestry Group ; Cardia ; Epidemiology ; Female ; Humans ; Incidence ; Male ; Registries ; Stomach Neoplasms ; United States

Objective To investigate the ultrasonography discrepancy of hepatic neuroendocrine neoplasm ( hNEN ) derived from different primary locations and pathological grades . Methods From August 2010 to April 2016 ,50 consecutive patients with 54 hNENs confirmed by pathology and imaging diagnosis underwent baseline ultrasound ( BUS ) and contrast-enhanced ultrasound ( CEUS ) in the First Affiliated Hospital of Sun Yat-sen University were enrolled in the retrospective study . On the basis of primary sites ,all hNENs were divided into three groups :pancreas ,gastrointestinal tract and other location groups . According to the pathological grading ,the hNENs were divided into hNET ( hepatic neuroendocrine tumor) group and hNEC ( hepatic neuroendocrine carcinoma) group . The imaging features of BUS and CEUS were retrospectively investigated and the ultrasonography discrepancy of hNEN derived from different primary focus and pathological grades were compared . Results ① Comparison of hNEN derived from different primary sites :hNEN derived from pancreas and gastrointestinal tract were smaller than hNEN derived from other sites[ ( 3 .8 ± 2 .6) cm vs ( 8 .7 ± 7 .0) cm , P = 0 .037 ;( 2 .9 ± 2 .1) cm vs ( 8 .7 ± 7 .0) cm , P = 0 .005] ,but the difference between the pancreas and gastrointestinal tract was not statistically significant ( P = 1 .0 ) . As for the pattern of CEUS enhancement ,hNEN derived from pancreas and gastrointestinal tract usually showed homogenous enhancement ( 13/19 ,15/23) while hNEN derived from other primary sites usually showed heterogeneous enhancement ( 10/13) ,and the difference was statistically significant ( P = 0 .025) . ② Comparison of hNET and hNEC :the distinction of enhancement level in the portal phase of contrast-enhanced ultrasound was statistically significant ( P = 0 .033) . All hNEC appeared hypo-enhancement ,while a small part of hNET ( 7/31 ) appeared iso-enhancement .More hNEC lesions showed heterogenous enhancemnt than hNET in the arterial phase ( 14/21 vs 9/31 , P = 0 .007) ,and there were less hNEC lesions presented tumor bleeding vessels than hNET ( 8/21 vs 22/31 , P = 0 .019 ) . Conclusions hNEN derived from pancreas and gastrointestinal tract are in a manner similar to hNEN derived from other primary sites on ultrasonography , so it' s difficult to identify in ultrasound . The ultrasonographic features of hNEC are more resemble to malignancy and it can be distinguished from hNET .

Objective To analyze the features of hepatic neuroendocrine neoplasm ( HNEN ) with conventional ultrasound and contrast-enhanced ultrasound sonography (CEUS) ,and to evaluate the value in the diagnosis and differential diagnosis of HNEN by ultrasound . Methods Fifty patients of HNEN confirmed pathologically or clinically were enrolled . All patients underwent conventional ultrasound and CEUS . Among the patients ,5 cases were primary hepatic neuroendocrine neoplasm ( PHNEN) ,and 45 cases were metastatic hepatic neuroendocrine neoplasm ( MHNEN) . Conventional ultrasound and CEUS features of HNEN were analyzed and the distinctions between PHNEN and MHNEN were compared . Results Baseline ultrasound showed that 37 (74％ ) HNEN were multiple lesions located in liver ,23 ( 46％ ) lesions with hyperechoic appearance ,35 ( 70％ ) lesions with homogeneous echoic ,28 ( 56％ ) lesions were clearly marginated ,8 (16％ ) lesions were surrounded by acoustic halo ,and 12 ( 24％ ) lesions with posterior echo attenuation . CEUS showed that the majority of HNEN exhibited the enhanced pattern of rapid wash-in and wash-out" . Forty-six ( 92％ ) lesions showed hyper-enhancement in the arterial phase ,44 ( 88％ ) lesions showed iso-enhancement in the portal phase ,and 47 ( 94％ ) lesions showed hypo-enhancement in the late phase .Feeding vessels were observed in 31 ( 62％ ) lesions ,intralesional non-enhancement zone was observed in 17(34％ ) lesions ,and capsule enhancement in the delay phase was found in 10( 20％ ) lesions . MHNEN had smaller diameter [ ( 3 .92 ± 2 .77) cm vs (12 .82 ± 8 .85) cm , P = 0 .004] and less likely to present cystic structure intralesional than PHNEN ( 1/45 vs 2/5 , P < 0 .001 ) . The differences of other baseline ultrasonographic characteristics ,enhanced characteristics and enhanced time on CEUS between PHNEN and MHNEN were not statistically significant ( all P > 0 .05) . Conclusions HNEN has a certain characteristic that can be identified on ultrasonography . Ultrasound can provide some valuable information to diagnose HNEN . While it′s difficult to differentiate PHNEN and MHNEN owing to their similar ultrasonographic characteristics .