ObjectiveThis study sought to investigate the impact of exosomes derived from LoVo cells (LoVo-Exos) in colorectal cancer (CRC) on tumor angiogenesis, as well as to elucidate the potential molecular mechanisms underlying their pro-angiogenic effects. MethodsLoVo-Exos were isolated via ultracentrifugation, and their internalization into recipient human umbilical vein endothelial cells (HUVECs) was visualized using confocal microscopy. The influence of LoVo-Exos on angiogenesis was assessed through an in vitro tube formation assay. Additionally, the pro-angiogenic effects of LoVo-Exos were evaluated in vivo using a matrix gluing assay in mice. To investigate the molecular mechanisms through which LoVo-Exos facilitate angiogenesis, Western blot analysis was employed to examine the transfer of pEGFR by LoVo-Exos into recipient cells. Both Western blot and ELISA were utilized to assess the expression levels of key signaling proteins within the EGFR-ERK pathway, as well as the expression of downstream angiogenic core molecules. Furthermore, the impact of EGFR knockdown and ERK inhibitor treatment on angiogenesis was evaluated, with subsequent analysis of the expression of downstream angiogenic core molecules following these interventions. ResultsConfocal microscopy demonstrated the internalization of LoVo-Exos into HUVECs. In vitro angiogenesis assays further indicated that LoVo-Exos significantly enhanced the formation of tubular structures in HUVECs. Additionally, macroscopic examination of subcutaneous matrix plug formation in mice revealed a substantial increase in vascular-like structures within the matrix plugs following the administration of LoVo-Exos, compared to the PBS control group. Hematoxylin and eosin (HE) staining revealed the presence of erythrocyte-filled microvessels within the matrix plugs combined with LoVo-Exos. Furthermore, immunohistochemical analysis demonstrated the expression of the endothelial cell marker CD31 in these matrix plugs. The presence of CD31-positive cells in the LoVo-Exos-treated matrix plugs was associated with a significant enhancement in the formation of luminal structures. These findings suggest that LoVo-Exos facilitate the in vivo development of vascular-like structures. Subsequent investigations demonstrated that LoVo-Exos facilitated the delivery of pEGFR to HUVEC, thereby enhancing angiogenesis. Conversely, LoVo-Exos with EGFR knockdown exhibited a diminished capacity to promote angiogenesis, an effect that was further attenuated by the ERK phosphorylation inhibitor U0126. Western blot analysis assessing the activation of the EGFR-ERK signaling pathway in HUVEC indicated that LoVo-Exos augmented angiogenesis through the activation of this pathway. Furthermore, analysis of the impact of LoVo-Exos on the expression of downstream angiogenic core molecules revealed an increase in interleukin-8 (IL-8) secretion in HUVEC. The enhancement observed was diminished in LoVo-Exos following EGFR knockdown, and this reduction was counteracted by the ERK phosphorylation inhibitor U0126. ConclusionThe underlying mechanism may involve the delivery of pEGFR in LoVo-Exos to HUVECs, leading to increased IL-8 secretion via the EGFR-ERK signaling pathway, thereby enhancing the angiogenic potential of HUVECs. This finding may offer new insights into the mechanisms underlying cancer metastasis.

OBJECTIVE: To retrospectively analyze the clinical characteristics of 15 children with B-cell acute lymphoblastic leukemia (B-ALL) treated with blinatumomab, and summarize the efficacy and safety of blinatumomab in the treatment of pediatric B-ALL. METHODS: Fifteen children who received treatment with blinatumomab from February 2022 to January 2023 were enrolled in this study. One course (28 days) of blinatumomab concurrent with intrathecal chemotherapy was given according to the standard regimen, except for 2 cases who had shortened course of treatment due to hematopoietic stem cell transplantation (HSCT) and did not receive combined intrathecal chemotherapy, and 1 case had a shortened course of treatment due to economic problems. The efficacy and safety of the treatment were evaluated. RESULTS: In terms of efficacy, for the children who had achieved complete molecular remission (CMR) before treatment, blinatumomab treatment could effectively maintain CMR status; For the children who did not achieve CMR, the CMR rate after one standard course of treatment with blinatumomab reached 66.7%(4/6); For the children with relapsed/refractory ALL (R/R ALL) who had minimal residual disease (MRD), the MRD clearance rate reached 75.0%(3/4). The statistical results of the incidence of adverse events showed that 13.3%(2/15) of the children did not experience any adverse events. The most common adverse events were cytokine release syndrome (CRS) (73.3%, 11/15) and transaminase elevation (26.7%, 4/15); 33.3%(5/15) of the children experienced grade 3 or higher adverse events. All the adverse events were resolved after symptomatic treatment.The level of IgG decreased significantly after 4-7 weeks of treatment with blinatumomab, and gradually recovered after 8 weeks of treatment. CONCLUSION Blinatumomab can be used as a safe and effective treatment for inducing deep remission in pediatric R/R-ALL patients and as a bridge therapy for the pediatric ALL patients who are intolerant to chemotherapy.
Humans ; Antibodies, Bispecific/therapeutic use* ; Child ; Retrospective Studies ; Female ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Remission Induction ; Treatment Outcome ; Child, Preschool ; Adolescent ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

OBJECTIVE: To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS: Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS: The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans ; Lymphoma, T-Cell, Peripheral/pathology* ; Prognosis ; Retrospective Studies ; Central Nervous System Neoplasms/pathology* ; Neoplasm Invasiveness ; Male ; Female ; Central Nervous System/pathology* ; Middle Aged ; Adult

Migratory birds are found worldwide.These birds are natural carriers of pathogens,because of their long-distance mi-grations across different climatic and geographic regions.The pathogens carried by migratory birds can enter ecosystems along migra-tory routes through direct and indirect contact between animal hosts,thereby potentially threatening the health of local poultry and even humans.Herein,we systematically analyzed evidence of pathogen spillover between migratory birds and poultry,and summa-rized the three modes of long-distance pathogen transmission by migratory birds(internal carriage,surface carriage,and environmen-tal contamination),as well as the two pathways of pathogen spillover between migratory birds and poultry(direct contact and indirect contact).Furthermore,this study proposes a multi-tiered mitigation strategy,grounded in the One Health framework,for targeting animal-environment-human interfaces to decrease the pathogen transmission risks associated with migratory birds.Key interventions include establishing an early-warning surveillance system for migratory flyways,enhancing biosecurity protocols in poultry production systems,and developing cross-regional risk assessment models for pathogen spread.Our findings provide critical theoretical founda-tions and empirical evidence for preventing zoonotic disease emergence and safeguarding sustainable poultry production.This inte-grated approach advances the coordinated development of biosafety measures and global health security.

This study analyzed the genetic evolutionary characteristics of sandflies and their effects on the spread of kala-azar in various environments in endemic provinces in China,to provide a scientific basis for kala-azar disease prevention and control.Sand-flies were collected in kala-azar endemic areas such as southern Xinjiang,the large hilly areas of southern Gansu,the northern Sich-uan and Taihang Mountains,and surrounding small hills.The cytochrome c oxidase subunit I and cytochrome b gene fragments of mito-chondrial DNA were amplified to identify sandfly species.The COI and Cytb gene sequences of sandflies from southern Xinjiang and Si-chuan recorded in NCBI were also collected.The intraspecific and interspecific genetic differences of sandflies were calculated in MEGA11.0,and a phylogenetic tree was constructed through the neighbor-joining method,for analysis of the genetic and evolutionary characteristics of sandfly populations and their effects on disease transmission.A total of 155 sandflies were collected from nine sam-pling sites in seven provinces of China;the species included Phlebotomus chinensis,Phlebotomus wui,and Sergentomyia squamirostris.Five sandfly species belonging to two genera were collected:P.chinensis,P.wui,and Phlebotomus alexandri in the genus Phleboto-mus,and S.squamirostris in the genus Sergentomyia.Genetic evolution analysis based on COI and Cytb gene sequences indicated intra-specific genetic distances of 0-0.062 and 0-0.056,respectively,and interspecific genetic distances of 0.126-0.176 and 0.110-0.171,respectively.The phylogenetic tree indicated that P.wui,P.alexandri,Phlebotomus longiductus,and S.squamirostris clus-tered into one branch.The sequences of P.chinensis in the large and small hilly areas clustered into two geographical clades.In the small hilly areas,the sequences of P.chinensis aggregates showed small genetic differences,the pathogen infection was consistent,and the cases showed an epidemic spread trend.Large genetic differences at the molecular level were observed among sandflies in dif-ferent ecological regions,thus indicating key effects on leishmaniasis transmission.On the basis of these findings,prevention and con-trol strategies should be adapted to local conditions,and precise and effective prevention and control measures should be formulated according to the genetic evolution characteristics of sandflies in different regions,to better control the transmission of Kala-azar.

Objective:To investigate the role of SiHa cell-derived exosomal hsa-miR-29c-3p in the angiogenesis of cervical cancer(CC).Methods:Cancer tissue specimens from 45 patients with cervical squamous cell carcinoma(CSCC)and normal cervical tissue specimens from 15 controls were collected from Department of Gynecology,Hengyang Central Hospital from January 2019 to December 2021.CSCC SiHa cells and human umbilical vein endothelial cells(HUVECs)were routinely cultured.miRNA-NC,hsa-miR-29c-3p,si-miRNA-NC,and si-hsa-miR-29c-3p were transfected into SiHa cells with Lipofectamine 2000,grouped as miRNA-NC group,hsa-miR-29c-3p group,si-miRNA-NC group and si-hsa-miR-29c-3p group,respectively.HUVECs were transfected with mimic-NC,miR-29c-3p-mimic,pCMV-NC,and pCMV-ATAD2B(ATPase family protein 2B with AAA domain)using Lipofectamine 2000,grouped as the mimic-NC group,miR-29c-3p-mimic group,pCMV-NC group,pCMV-ATAD2B group,and pCMV-ATAD2B+miR-29c-3p-mimic group.The expression of hsa-miR-29c-3p in CSCC tissues was detected by in situ hybridization(ISH),and CD31-positive blood vessels in CSCC tissues and xenograft tissues were detected by immunohistochemistry(IHC).Exosomes from SiHa and C33a cells were isolated and characterized using transmission electron microscopy(TEM)and western blotting(WB).The uptake of exosomes by HUVECs was examined.The expression of hsa-miR-29c-3p and ATAD2B mRNA in SiHa and C33a cells,as well as in their derived exosomes,was detected using qPCR.Tube-forming assay,Transwell assay,and scratch healing assay were performed to detect the effect of exosomes on the ability of HUVEC migration and tube formation.Dual luciferase reporter gene assay verified the interaction between hsa-miR-29c-3p and ATAD2B.Xenograft experiments examined the effects of SiHa cell-derived exosomes on transplanted tumor growth and angiogenesis in each group.Results:hsa-miR-29c-3p was highly expressed in CSCC tissues and was positively correlated with microvessel density(MVD)(all P<0.05).Exosomes derived from SiHa and C33a cells exhibited typical exosomal morphology and protein expression patterns.Exosomal hsa-miR-29c-3p from SiHa and C33a cells were efficiently taken up by HUVECs in vitro.The SiHa cell-derived exosomal hsa-miR-29c-3p promoted not only the tube-forming and migration of HUVECs in vitro but also the xenograft growth and angiogenesis in vivo(all P<0.05).hsa-miR-29c-3p directly targeted ATAD2B and regulated its expression(P<0.05).Overexpression of ATAD2B reversed the promotive effect of hsa-miR-29c-3p on tube-formation,migration,and scratch-healing in HUVECs(all P<0.05).Conclusion:SiHa cell-derived exosomal hsa-miR-29c-3p regulates angiogenesis in CSCC tissues by targeting ATAD2B.Exosomal hsa-miR-29c-3p may be a potential diagnostic marker and therapeutic target for CC diagnosis and treatment.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

OBJECTIVE: Aloin, the main active component in Aloe vera (L.) Burm. f., has shown promising anti-tumor effects. This study investigated the impact of aloin in lung squamous cell carcinoma (LUSC) and explored its functional mechanism. METHODS: We analyzed the viability, migration, invasion, proliferation, and apoptosis of two LUSC cell lines after treatment with aloin. Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2 (NR3C2) were predicted by bioinformatics. The biological functions of NR3C2 and metallothionein 1 M (MT1M) in the malignant properties of LUSC cells were determined. A co-culture system of LUSC cells with monocyte-derived macrophages was constructed. Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo. RESULTS: Aloin suppressed malignant properties of LUSC cells in vitro. However, these effects were negated by the silencing of NR3C2. NR3C2 was found to activate MT1M transcription by binding to its promoter. Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing. Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages, whereas NR3C2 silencing led to reverse trends. Consistent findings were reproduced in vivo. CONCLUSION This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization. Please cite this article as: Chen YN, Lu JY, Gao CF, Fang ZR, Zhou Y. Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis. J Integr Med. 2025; 23(2): 195-208.
Lung Neoplasms/metabolism* ; Humans ; Animals ; Cell Line, Tumor ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Macrophages/drug effects* ; Emodin/analogs & derivatives* ; Metallothionein/genetics* ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; Apoptosis/drug effects* ; Receptors, Glucocorticoid/genetics*