Integrin α _v β ₃ is overexpressed in various tumor cells and angiogenesis. To date, no drug has been proven to target it for therapy. A first-in-human study was designed to investigate the safety, pharmacokinetics, and dosimetry of ¹⁷⁷Lu-AB-3PRGD2, a novel integrin α _v β ₃-targeting radionuclide drug with an albumin-binding motif to optimize the pharmacokinetics. Ten patients (3 men, 7 women; aged 45 ± 16 years) with integrin α _v β ₃-avid tumors were recruited to accept ¹⁷⁷Lu-AB-3PRGD2 injection in a dosage of 1.57 ± 0.08 GBq (42.32 ± 2.11 mCi), followed by serial scans to obtain its dynamic distribution in the body. Safety tests were performed before and every 2 weeks after the treatment for 6-8 weeks. No adverse event over grade 3 was observed. ¹⁷⁷Lu-AB-3PRGD2 was excreted mainly through the urinary system, with intense radioactivity in the kidneys and bladder. Moderate distribution was found in the liver, spleen, and intestines. The estimated blood half-life was 2.85 ± 2.17 h. The whole-body effective dose was 0.251 ± 0.047 mSv/MBq. The absorbed doses were 0.157 ± 0.032 mGy/MBq in red bone marrow and 0.684 ± 0.132 mGy/MBq in kidneys. This first-in-human study of ¹⁷⁷Lu-AB-3PRGD2 treatment indicates its promising potential for targeted radionuclide therapy of integrin α _v β ₃-avid tumors. It merits further studies in more patients with escalating doses and multiple treatment courses.

Mammalian target of rapamycin inhibitor (mTORi) not only exert strong immunosuppressive effects, but also possess multiple potential benefits, including antiviral, antitumor, antifibrotic, and anti-aging properties. Their long-term efficacy in the field of organ transplantation has been well established, and they have been widely applied in clinical practice. However, the adverse effects of mTORi-such as impaired wound healing, oral ulcers, anemia, proteinuria, hyperglycemia, dyslipidemia, pneumonia, lymphedema, and angioedema-remain a challenge in clinical settings. In immunosuppressive regimens for organ transplantation, mTORi are used in diverse combination therapies and exhibit considerable inter-individual variability. This article briefly reviews recent research progress on mTORi in solid organ transplantation (SOT) and discusses strategies for their rational application, aiming to provide useful insights for clinical practice.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

Cardiovascular disease caused by radiotherapy(RT)is the most common cause of non-neoplastic death in cancer patients.Having advantages of dynamic observation and no radiation,echocardiography has been widely used in evaluating heart structure and function of patients after RT,which has become the preferred imaging method for screening,diagnosing and monitoring radiation-induced heart disease(RIHD).The research progresses of echocardiography in evaluating RIHD were reviewed in this article.

Objective:To investigate the expression characteristics of Zeste enhancer of Zeste homolog 2 (EZH2) in breast cancer tissue and its influence on tumor progression and prognosis.Methods:Transcriptome data of breast cancer tissue and normal breast tissue adjacent to cancer as well as clinical data of patients were obtained from the cancer genome atlas (TCGA) database, gene expression comprehensive database and European genome phenotype archives database, and the difference of EZH2 expression was analyzed using TIMER 2.0 platform. The survival information of breast cancer patients was obtained from the Kaplan Meier Plotter database, and the overall survival time, relapse free survival time and distant metastasis free survival time of breast cancer patients with low EZH2 expression and high EZH2 expression were compared. Select 14 nude mice were selected and randomly divided into si-EZH2 group and control group, with 7 mice in each group.MCF7 culture suspensions transfected with EZH2 knockdown plasmid and control plasmid were inoculated for corresponding group. The body mass and tumor volume of two groups of nude mice inoculated with MCF7 cells were compared at different times. On the 28th day, the nude mice were euthanized and the tumors were dissected to compare the tumor mass of the two groups of nude mice. The normally distributed quantitative data was represented by xˉ ± s. Two independent sample t-tests were used for comparison between two groups, repeated measures ANOVA was used for comparison of body mass and tumor volume between two groups of nude mice at different times, and Bonferroni test was used for pairwise comparison. The comparison of survival rates was conducted using log rank test. Results:A total of 1085 breast cancer tissues and 291 normal adjacent breast tissues were included in the TCGA database. EZH2 expression in breast cancer tissues was higher than that in normal adjacent breast tissues ( P<0.05). In the Kaplan Meier Plotter database, the total survival time, relapse free survival time, and distant metastasis free survival time of breast cancer patients in the EZH2 overexpression group were shorter than those in the EZH2 low expression group ( P=0.013, <0.001, <0.001). After 7 days of inoculation with MCF7 culture suspension, significant subcutaneous tumors were observed on the left back of both groups of nude mice. On the first day, there were no statistically significant difference in body mass between the two groups of nude mice ( P>0.05); On day 7, 13, 19, 25, and 28, the body mass and tumor volume of both groups of nude mice gradually increased (nude mouse body mass: within group F=29.31, P<0.001, between groups F=234.32, P<0.001, Finteraction=16.83, P<0.001; Tumor volume: within group F=34.00, P<0.001, between groups F=193.17, P<0.001, Finteraction=35.61, P<0.001). And the body mass of the siEZH2 group nude mice was higher than that of control group (all P<0.05). On days 19, 25, and 28, tumor the volume of the siEZH2 group nude mice was smaller than that of control group (all P<0.05). On the 28th day, the mass of tumors dissected in the siEZH2 group of nude mice was lower than that in the control group [(0.30±0.07) g vs. (0.61±0.14) g, t=5.16, P<0.001]。 Conclusions:EZH2 is highly expressed in breast cancer tissues and is significantly associated with poor prognosis. Knockdown of EZH2 can significantly inhibit the proliferation and tumor formation of breast cancer cells.

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

Objective:To improve the understanding of anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma complicated with hemophagocytic syndrome (HPS) in children.Methods:A retrospective analysis was conducted on the diagnosis and treatment of a case of EB virus-associated ALK-negative anaplastic large cell lymphoma in a child with HPS as the clinical manifestation at Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University in December 2019, and literature review was conducted.Results:The patient was an 8-year-old boy who was admitted with facial yellowing and recurrent fever. After comprehensive examination, he was diagnosed with HPS. After 2 weeks of chemotherapy according to the hemophagocytic lymphohistiocytosis (HLH)-1994 regimen, lymph node biopsy was performed. Immunohistochemistry showed that CD30, CD5, CD4, CD7, EMA, TIA-1, and VIM were positive, ALK, CD2, CD3, CD8, CD117, CD20, INI-1, CD68, MyoD1, Myogenin, Desmin, Langerin, SALL4, CD56, GramB, and CK were negative, LCA was weakly positive, TFE3 was partially weakly positive, and Ki-67 positivity index was 90%. The clonality assay for TCRD gene rearrangement was positive. The supplementary diagnosis was ALK-negative anaplastic large cell lymphoma, and the clinical risk stratification was classified as high-risk group. After 2 courses of chemotherapy with the South China Children's Cancer Group-non-Hodgkin lymphoma 2017 regimen (SCCCG-NHL-2017), he was evaluated as complete remission (CR), and after 6 courses, he was still evaluated as CR. The patient received autologous hematopoietic stem cell transplantation. The patient was followed up until May 2024, his survival status was good.Conclusions:EB virus-associated ALK-negative anaplastic large cell lymphoma complicated with HPS in children is rare, chemotherapy combined with autologous hematopoietic stem cell transplantation is a feasible treatment option.

Objective:To utilize single-cell RNA sequencing (scRNA-seq) to untangle the temporal expression profiles of molecules associated with congenital tooth agenesis and dental hard tissue formation during mouse molar development, and to construct a comprehensive cell atlas spanning the entire developmental period from E13.5 to P7.5, thereby providing new insights into the molecular mechanisms underlying abnormal tooth development.Methods:scRNA-seq data of murine mandibular molar tooth germs at five developmental stages (E13.5, E14.5, E16.5, P3.5, P7.5) were obtained from the GEO database (accession: GSE189381). The Seurat pipeline was employed for quality control, data normalization, dimensionality reduction, and Harmony-based batch effect correction. Cellular subpopulations were identified through uniform manifold approximation and projection dimensionality reduction, while developmental trajectories were reconstructed using Monocle for pseudotime analysis.Results:scRNA-seq analysis profiling identified 27 distinct cellular clusters, which were annotated into twelve major cell types including epithelial cells, mesenchymal cells, and endothelial cells. Msx1 exhibited a bimodal expression pattern. Pax9 reached its peak at E14.5 and then gradually decreased. Eda had a low expression level with a diffuse distribution. In contrast, Amelx and Enam were barely expressed during the embryonic stage and were activated at P3.5. Dspp was ectopically highly expressed in epithelial cells from P3.5 to P7.5, while Dmp1 was specifically upregulated in mesenchymal cells at P7.5.Conclusions:The temporal expression patterns of key regulatory genes for tooth agenesis (Msx1, Pax9, Eda), ameloblast differentiation (Amelx, Enam), and odontoblast development (Dspp, Dmp1) during mouse molar development. These findings provide a theoretical foundation and potential therapeutic targets for deciphering the molecular mechanisms underlying tooth agenesis and other developmental dental anomalies, paving the way for targeted clinical interventions.

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Objective To explore the application efficacy and complication occurrences of Tubridge embolization device(TED)and Pipeline embolization device(PED)in the treatment of elderly pa-tients with complex intracranial aneurysm(ICA).Methods A total of 119 elderly patients with complex ICA admitted in our hospital from January 2021 to July 2023 were enrolled,and accord-ing to different devices they used,they were divided into a TED group(n=71)and a PED group(n=48).Device delivery and complications were observed,digital subtraction angiography(DSA)was performed intra-and post-operatively to evaluate the embolization of aneurysms(Raymond grading),and modified Rankin scale(mRS)was adopted to assess the clinical symptoms and prognosis before and at 3 and 6 months after surgery.DSA was applied again at 6 months post-operatively to evaluate the effectiveness of treatment.DSA and magnetic resonance angiography were carried out to record aneurysm images during the follow-up of 3,6 and 12 months after sur-gery.Results There were no statistical differences between the TED group and PED group in terms of the success rate of device delivery and the incidences of intraoperative and postoperative complications,of the intraoperative and postoperative Raymond grades,and of the mRS scores be-fore surgery and at 3 and 6 months after surgery,and of the O-Kelly-Marotta grades and effec-tiveness at 6 months after surgery(P＞0.05).At 3,6 and 12 months after surgery,the complete occlusion rate was 64.8％,63.8％and 69.4％respectively in the TED group,and 70.8％,71.7％and 72.5％respectively in the PED group,and there was no significant difference in the rate be-tween the two groups(P＞0.05).Conclusion TED and PED have similar efficiencies in the suc-cess rate of operation,safety,aneurysm embolization efficacy,immediate and long-term efficacies,and neurological function prognosis in the elderly patients with complex ICA.There exists a cer-tain risk of intraoperative and postoperative complications.Clinically,appropriate blood flow guid-ing devices should be selected based on the patient's actual condition.