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Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective To construct CD19-targeted chimeric antigen receptor natural killer(CAR-NK)cells armored with interleukin15(IL15)or IL15 receptor-linker(RLI)and preliminarily validate their proliferative capacity and anti-tumor activity in vitro.Methods Natural killer cells(NK92 and NK92MI)from patients with human malignant non-Hodgkin lymphoma were cultured,and CD19-targeted CAR-NK cells armored with IL15 or RLI were prepared using retroviral vector particles.IL15 secretion was measured by ELISA,and proliferative capacity was assessed via CFSE dilution assays.Human B-lymphocytic leukemia cells(Nalm6-GFP-Luc)and human colon cancer cells overexpressing CD19(hCD19-SW620-GFP-Luc)were cultured,with surface CD19 expression confirmed(>99%positivity for both).Anti-tumor activity was evaluated by measuring cytotoxicity at effector-to-target(E:T)ratios using luciferase-based assays(4/12 h),detecting surface CD107a expression via flow cytometry,and quantifying cytokine release using CBA assays.Results NK92/NK92MI-CD19 CAR cells armored with IL15 or RLI were successfully generated.IL15 secretion was significantly higher in armored groups versus non-armored controls(P<0.01).Without IL-2 stimulation,IL15/RLI enhanced CAR-NK proliferation(P<0.05).Both armored designs significantly increased tumor-killing efficiency(P<0.05)and CD107a degranulation.IL15/RLI-armored NK92-CD19 CAR cells exhibited elevated release of IL2,IL10,IL6,TNF-α,sFas,IFN-γ,and Granulysin(P<0.05),while armored NK92MI-CD19 CAR cells showed additional increases in Granzyme A,Granzyme B,and Perforin(P<0.05).Conclusion IL15/RLI-armored NK92/NK92MI-CD19 CAR cells demonstrate potent anti-tumor activity,supporting their combined clinical therapeutic potential for tumors.

The management of chronic wounds presents significant challenges, characterized by a low rate of healing and substantial impairment of patients’ quality of life, while also exerting a considerable strain on healthcare resources. Wound healing is a multifactorial and dynamic process, necessitating close monitoring of wound changes and timely, appropriate interventions. Smart bandage/dressing, an innovative approach born from interdisciplinary research, offers a new generation of wound care. It enables dynamic quantitative monitoring of wound conditions; facilitates transdermal drug release and physical mode therapeutics; and adjusts interventions in real time based on monitoring outcomes. In comparison to traditional wound dressings, smart bandages exhibit attributes such as real-time responsiveness, precision, and convenience. They not only simplify wound management but also enhance patient comfort and compliance, showcasing potential as a safe and effective treatment modality. Smart bandages hold promise for elevating the efficiency of managing chronic wounds, reducing morbidity rates, alleviating the burden of disease, and ultimately improving patients’ quality of life. This paper summarized the recent research progress of smart bandages and provided insights into novel wound care strategies.

Objective:To investigate the clinicopathological features, immunophenotype, diagnosis and differential diagnosis of SRF-rearranged cellular perivascular myoid tumor.Methods:Two cases of SRF-rearranged cellular perivascular myoid tumor diagnosed in the Department of Pathology, Fudan University Shanghai Cancer Center from October 2021 to March 2022 were collected. Immunohistochemical staining, fluorescence in-situ hybridization (FISH) and next-generation sequencing (NGS) were performed, and the literature was reviewed.Results:Case 1, a 3-month-old boy presented with a painless tumor of the scalp, measuring about 2 cm in diameter. Case 2, a 3-year-old girl complained with a painless tumor of the knee, measuring approximately 1.5 cm in diameter. Microscopically, the tumor had a clear boundary and showed multinodular growth. The tumor was mainly composed of spindle cells arranged in long intersecting fascicles associated with thin, slit-like or branching ectatic vessels, focally forming hemangiopericytoma-like appearance. The tumor cells were abundant, but there was no obvious atypia. Mitotic figures (3-4/10 HPF) were noted. H-caldesmon and SMA were positive in both cases. Case 1 showed diffuse and strong positivity for Desmin, and focally for CKpan. Ki-67 proliferation index was 20% and 30%, respectively. FISH displayed NCOA2 gene translocation in case 1 and the RELA gene translocation in case 2. NGS detected the SRF-NCOA2 gene fusion in case 1 and the SRF-RELA gene fusion in case 2. Both patients underwent local excisions. During the follow-up of 5-14 months, case 1 had no local recurrence, while case 2 developed local recurrence 1 year post operatively.Conclusions:SRF-rearranged cellular perivascular myoid tumor is a novel variant of perivascular cell tumor, which tends to occur in children and adolescents. The tumor forms a broad morphologic spectrum ranging from a pericytic pattern to a myoid pattern, and include hybrid tumors with a mixture of pericytic and myoid patterns. Due to its diffuse hypercellularity and increased mitotic figures and smooth muscle-like immunophenotype, the tumor is easy to be misdiagnosed as myogenic sarcomas. The tumor usually pursues a benign clinical course and rare cases may locally recur.

Objective To construct Raji-Luc lymphoma cells with CD19 knockout using CRISPR/Cas9 technology and preliminarily validate their immune escape ability.Methods PB-CRISPR-CD19 small guide RNA(sgRNA)plasmids was constructed,the optimal sgRNA sequence was screened,and Raji-Luc cells with pCAG-PBase,PB-CD19 sgRNA,and PB-CRISPR-Cas9 were co-transfected.Stable knockout monoclonal cell lines were screened by flow sorting and limit dilution method and the knockout effect was verified through gene sequence testing.The expression of luciferase on the surface of the cell line was detected by microplate reader,CD19 CAR-T and CD38 CAR-T previously constructed in the laboratory were used as effector cells,and the immune escape ability of Raji-Luc CD19 KO cell line was verified by universal luciferase chemiluminescence method.Results The transfection efficiency of Raji-Luc CD19 KO cells prepared by electro transfection was high,and the knockout efficiency of the two monoclonal cells was more than 99%.There was no significant difference in luciferase expression compared to the original Raji-Luc cells,and CD19 CAR-T cells could not be activated to the kill them.Conclusion Successfully constructed Raji-Luc CD19 KO lymphoma cell line.

Objective To explore the effect of sling exercise with Tuina therapy on kinesiophobia in old patients with lumbar disc herniation,and analyze the mechanism based on brain-bone axis. Methods A total of 56 old patients with chronic lumbar disc herniation and kinesiophobia were selected from the Reha-bilitation Hospital of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from September,2022 to December,2023;and randomly divided into control group(n=28)and experimental group(n=28).The control group accepted conventional exercise therapy,while the experimental group accepted sling exercise with Tuina therapy,for four weeks.They were assessed with simplified Chinese version of Tampa Scale of Kinesiophobia(TSK),Japanese Orthopaedic Association score(JOA)and Visual Analogue Scale for pain(VAS)before and after treatment,while the bone mineral density(BMD)was tested,the levels of osteoprote-gerin(OPG),norepinephrine(NE)and corticosteroids(Cor)in serum were measured,and the median frequency(MF)of weak-link erector spinae was detected with surface electromyography. Results Two cases dropped off in the control group,and one in the experimental group.The scores of all the assessment improved in both groups after treatment(|t|>14.168,P<0.001),as well as the serum levels of OPG,NE and Cor(|t|>2.103,P<0.05),BMD(|t|>2.726,P<0.05),and MF of erector spinae(|t|>14.736,P<0.001);all of them were better in the experimental group than in the control group(|t|>2.154,P<0.05). Conclusion Sling exercise with Tuina therapy can improve the pain and kinesiophobia of lumbar disc herniation in the old adults,which may promote the recovery of physical and mental function through regulating the levels of hor-mones and neurotransmitters related to the brain-bone axis.

The management of chronic wounds presents significant challenges, characterized by a low rate of healing and substantial impairment of patients’ quality of life, while also exerting a considerable strain on healthcare resources. Wound healing is a multifactorial and dynamic process, necessitating close monitoring of wound changes and timely, appropriate interventions. Smart bandage/dressing, an innovative approach born from interdisciplinary research, offers a new generation of wound care. It enables dynamic quantitative monitoring of wound conditions, facilitates transdermal drug release and physical mode therapeutics, and adjusts interventions in real time based on monitoring outcomes. In comparison to traditional wound dressings, smart bandages exhibit attributes such as real-time responsiveness, precision, and convenience. They not only simplify wound management but also enhance patient comfort and compliance, showcasing potential as a safe and effective new treatment modality. Smart bandages hold promise for elevating the efficiency of managing chronic wounds, reducing morbidity rates, alleviating the burden of disease, and ultimately improving patients’ quality of life. This paper summarized the recent research progress of smart bandages and provide insights into novel wound care strategies.

Improvement of the jawline contour is a key focus in lower face and neck rejuvenation treatments. Achieving a well-defined, smooth jawline is a shared goal for both patients and plastic surgeons. This article reviews recent research on age-related changes of the jawline and evaluation method, offering valuable references for jawline rejuvenation treatments.The jawline's unique anatomical position, coupled with age-related changes, involves dynamic alterations in bone, soft tissue, and skin across multiple layers, making rejuvenation of this area a complex and challenging task. In recent years, advances in imaging technologies such as two-dimensional photography, three-dimensional stereophotogrammetry, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and micro-CT have expanded the understanding of jawline anatomy and provided precise tools for analysis and evaluation.