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 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.

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 study the management effect of the intelligent management mode of anesthet-ic medicine box.Methods The intelligent reconstruction of the management mode of anesthesia box in the de-partment of surgical anesthesiology was carried out,and the differences in the taking and return time in 3-month before and after applying the medicine box intelligent management,error rate,and information tracking were compared,and the management effect of the medicine box was compared between the intelligent manage-ment and the traditional mode.Results The prescription modification rate,accounting error rate,discrepancy rate of person and box,and omission rate of registration had statistical differences between the traditional management mode and intelligent management mode(P<0.05).The single medicine box management work-ing time for anesthetist getting the medicine box,returning the medicine box,taking the refrigerator medicine,generating prescription and charge in intteligent management mode was shortened compared with the tradi-tional management mode,and the difference was statistically significant(P<0.05);the working time of drug management such as drug counting,prescription checking,registration records checking,drug adding and daily inventory checking in the intelligent management mode was shortened compared with the traditional manage-ment mode,and the difference was statistically significant(P<0.05).Conclusion Compared with the tradi-tional mode,the anesthetic box management intelligent mode has high efficiency and strong reliability,moreo-ver is more conducive to the standardized management of anesthetic drugs in the operating room.

Objective To explore the efficacy and safety of conversion therapy for advanced hepatocellular carcinoma(HCC)with macrovascular invasion.Methods A total of 149 patients with advanced HCC with macrovascular invasion who were treated at our hospital from Jul.2019 to Jun.2021 were enrolled.All patients received systemic therapy combined with local therapy,and were assigned to conversion therapy group(n=42)and non-conversion therapy group(n=107)according to whether they ultimately underwent surgical treatment.The long-term prognosis and adverse reactions of these patients after conversion therapy were analyzed.Results The median event-free survival of 149 patients was 15.5 months,and the median overall survival had not been reached.The median event-free survival in the conversion therapy and non-conversion therapy groups were 19.8 months and 10.7 months,respectively,with the median overall survival being not reached and 28.2 months,respectively.Multifactor Cox regression analysis showed that conversion therapy was a protective factor for overall survival(hazard ratio[HR]=0.125,95％confidence interval[CI]0.016-0.966),but not for event-free survival.The 1-year and 2-year overall survival rates of the conversion therapy and non-conversion therapy groups were 100.0％,96.4％and 72.1％,53.4％,respectively,and the difference in survival curves between the 2 groups was statistically significant(P=0.003).The 1-year and 2-year event-free survival rates were 77.5％,33.8％and 47.3％,31.5％,respectively.There was no significant difference in survival curves between the 2 groups(P=0.070).The differences of the overall incidences of targeted and immunotherapy-related adverse reactions in the conversion therapy group and non-conversion therapy group(66.7％[28/42]vs 72.0％[77/107],P=0.524)and the incidences of grade Ⅲ to Ⅳ adverse reactions(23.8％[10/42]vs 27.1％[29/107],P=0.681),were not statistically significant.Conclusion For patients with advanced HCC with macrovascular invasion,conversion therapy can significantly improve the prognosis without serious adverse reactions.

Objective To construct a prognostic model of future asthma exacerbation risk in adults by com-bining novel biomarkers of serum chitinase-3-like protein 1(YKL-40),dipeptidyl peptidase-4(DPP4)and conventional predictors.Methods Patients with asthma in the non-acute exacerbation phase were recruited from the People's Hospital of Yubei District of Chongqing,from March 2022 to May 2023.Baseline clinical da-ta collected included medical history,forced expiratory volume in the first second(FEV1)/forced vital capacity(FVC),percentage of predicted forced expiratory volume in the first second(FEV1％pred),blood eosinophil count(EOS),blood neutrophil count(NEU),fractional exhaled nitric oxide(FeNO),serum YKL-40,and ser-um DPP4,etc.The patients were followed for one year to gather data on asthma acute exacerbations and their timings as defined in this study.A COX proportional hazards regression model was used to construct a prog-nostic model for future asthma exacerbations,with internal validation and results presentation.Results A to-tal of 224 patients with asthma completed the study.During the one-year follow-up period,102 patients experi-enced acute exacerbations as defined in this study.Based on univariate COX regression,stepwise regression for variable selection,clinical significance,and model simplicity,asthma control test(ACT)score group,number of asthma exacerbations in the past year group,log10(YKL-40),log10(FeNO),log10(EOS),and FEV1％pred were the following predictors were included in the final model.The overall C-statistic of the model was 0.795(95％CI:0.754-0.836),the area under the curve at the 52-week follow-up was 0.879(95％CI:0.834-0.924),and the Brier score at the 52-week follow-up was 0.142(95％CI:0.117-0.168).The calibration curve was close to a slope of 1,and bootstrap validation suggested good stability of the prediction model.The model was presented using a Nomogram and a dynamic scoring table in a web APP,which can be used to predict the risk of asthma exacerbations within 52 weeks for individual patients.Conclusion The prediction model based on serum YKL-40,EOS,FeNO,the number of asthma exacerbation in the past year group,FEV1％pred and ACT scores group can accurately predict the probability of acute attacks in 52 weeks of asthma patients.

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

Objective To retrospectively assess the clinical efficacy of acupuncture at the Huiyin point combined with Qingdu wash solution in the treatment of high-risk HPV infection.Methods A total of 264 patients who were initially diagnosed with high-risk HPV infection at the University City Gynecology Department of Guang-dong Provincial Hospital of Traditional Chinese Medicine between January 2022 and June 2024 were enrolled in the study.These patients were divided into two groups based on predefined inclusion and exclusion criteria.The ob-servation group included 134 patients who received acupuncture at the Huiyin acupoint combined with Qingdu wash solution,while the control group consisted of 130 patients who did not receive any intervention.The treatment pe-riod lasted for three months,during which the short-term clinical efficacy and safety profile were evaluated.Results The HR-HPV clearance rates in the observation group at 3 months and 6 months were 61.9%and 65.7%,respectively,which were significantly higher than those in the control group(16.9%and 21.5%),and the differences between the two groups were statistically significant(P<0.001).Following a three-month treatment regimen,the rate of HR-HPV positive-to-negative conversion in the observation group was significantly higher than that in the control group,with a statistically significant intergroup difference(P<0.001).The improvement in tra-ditional Chinese medicine(TCM)-related symptoms was also significantly better in the observation group compared to the control group(P<0.05).During the follow-up period,no cases of recurrence were observed in the observa-tion group,whereas the recurrence rate in the control group was 1.5%.Furthermore,no adverse reactions were re-ported in the observation group throughout the treatment period.Conclusion Acupuncture at the Huiyin point,when combined with Qingdu wash solution,can enhance the therapeutic outcomes of high-risk HPV infection and demonstrates a favorable safety profile.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.