Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

This article presents the diagnosis and treatment processes, and morphological and genetic testing of Gongylonema pulchrum in a case with G. pulchrum found in the oral mucosa. In addition, this article reviews publications pertaining to G. pulchrum human infections by Chinese scientists during the recent 10 years and summarizes the demographic and clinical characteristics, location and number of parasites, diagnosis and treatment processes, and epidemiological surveys of cases infected with G. pulchrum, so as to provide insights into improving the diagnostic capability among clinicians.

BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Objective: To utilize machine learning(ML) algorithms to develop accurate and effective prediction models for TAC dose/weight-adjusted trough concentration(C0/D). Methods: Data were collected on 264 TAC blood concentration monitoring data from 72 patients undergoing kidney transplantation. The effects of population statistical data, clinical features, combined medication, and ultrasound feature parameters on TAC C0/D were analyzed. Features with a significance level less than 0.05 in the univariate analysis of TAC C0/D were selected for inclusion in the random forest(RF) algorithm to identify significant features. These features were interpreted using partial dependency plots. Five ML algorithms, including RF, support vector regression(SVR), extreme gradient boosting(XGBoost), decision trees(DT) and artificial neural networks(ANN), were employed to establish the TAC C0/D prediction model. Hyper-parameter tuning was performed on the RF model that performed the best. Results : Ten characteristic variables with importance scores>5 were retained and included in the ML model: transglutaminase, red blood cell count, blood urea nitrogen, weight, serum creatinine, renal segmental arterial resistance index, renal aortic resistance index, hematocrit, renal pelvic Young′s modulus value, and time after transplantation. The partial dependence plots showed that all 10 important variables screened were positively correlated with TAC C0/D. The tuned RF model outperformed the other models with aR2of 0.81, aRMSEof 43.93, and aMAEof 29.97. Conclusion The ML models demonstrate good performance in predicting TAC C0/D and provide innovative interpretations using partial dependence plot. The optimized RF model shows optimal performance and offers a novel tool for individualized medication adjustment for TAC in renal transplant patients.

Objective To investigate the value of quantitative parameters(Kep and Ktrans)of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI),in predicting perineural invasion(PNI)in peripheral prostate cancer(PCa).Methods The clinical and preoperative MRI data of 45 patients with peripheral PCa who underwent radical prostatectomy(RP)were analyzed retrospectively.According to the pathological results,the patients were divided into PNI group(n=27)and non-PNI group(n=18).Various parameters,including age,total prostate specific antigen(tPSA),Ktrans value,Kep value,apparent diffusion coefficient(ADC)value,prostate volume,maximum lesion diameter,and prostate-specific antigen density(PSAD)were compared between the two groups.Multivariate logistic regression analysis was used to identify independent predictors of PNI,and a joint prediction model was established.The DeLong test was used to compare differences in the area under the curve(AUC)between the joint prediction model and each independent predictor.Results The univariate analysis identified statistically significant differences in the tPSA,Ktrans value,ADC value,maximum lesion diameter,and PSAD between the two groups(P＜0.01).The multivariate analysis showed that the Ktrans value and the maximum lesion diameter were independent predictors of PNI,with AUC of 0.854 and 0.874,respectively(P＜0.01).The AUC of the joint prediction model for PNI diagnosis was 0.955(P＜0.001).The DeLong test showed that the AUC of the joint prediction model for PNI diagnosis was better than that of the Ktrans and the maximum lesion diameter(P＜0.05).Conclusion The Ktrans value can be used to predict PNI.Furthermore,the combination of the Ktrans value and the maximum lesion diameter is more effective for predicting PNI than traditional methods.This provides more reference basis for the selection of clinical treatment methods.

Objective To explore the expression of prohibitin(PHB)in tumor tissues and analyze its effect on the prognosis of patients with digestive system malignant tumor(DT)and its mechanism.Methods ①The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)database were used to compare the expression of PHB in tumor tissues and normal tissues.②Five pairs of gastric cancer and adjacent tissues and 5 pairs of colon cancer and adjacent tissues were collected,and RT-qPCR was used to verify the mRNA expression levels.③ RT-qPCR and Western blotting were used to verify the differential expression of PHB in normal gastric mucosa cells(GES-1),gastric cancer cells(AGS,MKN45 and HGC27),normal colon cells NCM-460 and human colon cancer cell line SW480.④R language was used to analyze the effect of PHB on the prognosis,tumor microenvironment,tumor mutation burden and microsatellite instability of DT patients.⑤CIBERSORT algorithm was used to study the correlation between PHB expression in tumor tissues and tumor immune cell infiltration.Gene Set Enrichment Analysis(GSEA)was used to explore the biological function of PHB.⑥R language was used to analyze the relationship between PHB and drug sensitivity.Results ①PHB was highly expressed in colon cancer,cholangiocarcinoma,esophageal cancer,liver cancer,rectal cancer and gastric cancer(P＜0.01).②RT-qPCR and Western blotting showed that PHB was highly expressed in the tissues and cell lines of gastric cancer(P＜0.01)and colon cancer(P＜0.01).③The differential expression of PHB was associated with poor prognosis of hepatocellular carcinoma(P=0.002).In cholangiocarcinoma,gastric cancer,pancreatic cancer,liver cancer and esophageal cancer,PHB was positively correlated with tumor mutation burden and microsatellite instability(P＜0.05).④PHB was positively correlated with M2 macrophages in colon cancer(P=0.03).In cholangiocarcinoma,it was positively correlated with activated CD4+memory T cells(P＜0.05).In esophageal carcinoma,it was positively correlated with activated hypertrophy(P=0.03).It was positively correlated with M0 and M2 macrophages and monocytes in hepatocellular carcinoma(P＜0.05).It was positively correlated with resting dendritic cells,eosinophils and activated CD4+memory T cells in rectal cancer(P＜0.05).It was positively correlated with M0 macrophages,activated mast cells,neutrophils,resting natural killer cells,activated CD4+memory T cells and follicular helper T cells in gastric cancer(P＜0.05).⑤PHB was mainly enriched in class I receptors,PPAR and calcium signaling pathways(P＜0.05).⑥ The expression of PHB was positively correlated with the sensitivity of 13 drugs,including ammonafide,prasinolide and abiraterone(P＜0.05).Conclusion The expression of PHB is significantly related to the infiltration of various immune cells in DT and poor prognosis in DT patients,which may become a new biomarker and potential immunomodulatory target of DT.

Background::Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood.Methods::We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results::Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity.Conclusion::In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.

Objective To investigate the expression of long non-coding RNA(lncRNA)LINC02695 in human retinal microvascular endothelial cells(HRMECs)in high glucose(HG)environment and its effect on the proliferation,migration and neovascularization of HRMECs.Methods HRMECs was divided into four groups:the normal glucose(NG)group(5.5 mmol/L),the HG group(30.0 mmol/L),the HG+LINC02695 silenced group(HG+si-LINC02695),and the HG+silenced control group(HG+si-NC).Real-time quantita-tive fluorescent PCR(qPCR)was used to detect the expression of LINC02695 and vascular endothelial growth factor(VEGF)mRNA in HRMECs of each group.The cell proliferation of each group was measured by Cell Counting Kit-8(CCK-8)method.The migration ability of cells in each group was detected by Transwell as-say.The tube forming ability of cells in each group was detected by tube forming experiment.Results The qPCR results showed that compared with the NG group,LINC02695 and VEGF were highly expressed in the HG group(P＜0.05).Compared with the HG group,VEGF mRNA expression level in the HG+si-LINC02695 group was significantly decreased(P＜0.05).The results of CCK-8 experiment showed that the proliferation ability of the HG group was significantly enhanced compared with the NG group(P＜0.05).Compared with the HG group,the cell proliferation ability of the HG+si-LINC02695 group was significantly decreased(P＜0.05).The results of Transwell experiment showed that the cell migration ability of the HG group was significantly increased compared with the NG group(P＜0.05).Compared with the HG group,the cell migration ability of the HG+si-LINC02695 group was significantly decreased(P＜0.05).The results of tube formation experiment showed that compared with the NG group,the tube formation ability of the HG group was significantly increased(P＜0.05).Compared with the HG group,canalization ability of cells in the HG+si-LINC02695 group was significantly decreased(P＜0.05).Conclusion LINC02695 may be involved in promoting the proliferation,migration and angiogenesis of HRMECs induced by HG.

Objective To investigate the impacts of cinobufotalin combined with docetaxel+cisplatin chemotherapy on the disease control and the level of vascular endothelial growth factor(VEGF)in serum of patients with non-small cell lung cancer.Methods Totally 70 patients with non-small cell lung cancer admitted to Zhejiang Veteran Hospital from March 2019 to March 2022 were included.They were randomly divided into combination group(cinobufotalin combined with docetaxel+cisplatin,n= 35)and control group(docetaxel+cisplatin chemotherapy alone,n=35).The disease control rates of two groups,serum VEGF level,carcinoembryonic antigen(CEA),cy-tokeratin 19(CK19)and carbohydrate antigen 125(CA125)were measured using ELISA;life quality of patients was evaluated with the KPS score;The adverse events between two groups were compared.Results The disease control rate in the combination group(33/35,94.29％)was higher than that that of control group(25/35,71.43％,)(P＜0.05).After treatment,the level of VEGF in both groups of patients decreased,and the KPS score increased(P＜0.05)especially in the combination group(P＜0.05).After treatment,the level of serum CEA,CA125,and CK19 of control group and combination group were obviously lower than those before treatment(P＜0.05),while those in the combination group were even lower(P＜0.05).The incidence of adverse events in the combination group(5/35,14.29％)was lower than that in the control group(13/35,37.14％)(P＜0.05).Conclusions Cinobufotalin combined with docetaxel+cisplatin chemotherapy as a potential new chemotherapy significantly reduces the level of VEGF and tumor biomarkers in serum factor,improves the life quality of patients.The combined therapy is proved tobe safe.