1.Tumor-intrinsic PRMT5 upregulates FGL1 via methylating TCF12 to inhibit CD8+ T-cell-mediated antitumor immunity in liver cancer.
Jiao SUN ; Hongfeng YUAN ; Linlin SUN ; Lina ZHAO ; Yufei WANG ; Chunyu HOU ; Huihui ZHANG ; Pan LV ; Guang YANG ; Ningning ZHANG ; Wei LU ; Xiaodong ZHANG
Acta Pharmaceutica Sinica B 2025;15(1):188-204
Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8+ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8+ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.
2.Characteristics of asymptomatic HBV infection in HBsAg-positive blood donors from Dalian
Yingying WANG ; Xuelian DENG ; Xiaohan GUO ; Huihui GAO ; Peng SUN ; Dan LIU ; Daniel CANDOTTI ; Bing WANG
Chinese Journal of Blood Transfusion 2025;38(10):1361-1369
Objective: To analyze serological and molecular characteristics of asymptomatic HBV infection in HBV surface antigen positive (HBsAg+) blood donors from Dalian. Methods: The prevalence of HBsAg was analyzed among blood donors in Dalian between 2013 and 2022. Randomly selected HBsAg+ blood samples were subjected to HBV serological testing, HBV viral DNA quantification, and HBV genotyping. Results: Over this ten-year period, the prevalence of HBsAg decreased from 1.25% to 0.50% among blood donors in Dalian. Donors who tested positive for HBsAg prior to donation using a rapid test (RT) accounted for 92.5% of all HBsAg+ donors identified. A total of 240 confirmed HBsAg+ blood donors were randomly selected, including 125 donors with positive results and 115 with negative results in the pre-donation rapid test. HBsAg+ donors were mainly males (71.2%), with a median age of 42, and 97.5% of them being first-time donors. Based on HBV serological profiles, three stages of infection were identified: early infection (2.9%), suspected acute hepatitis (0.8%), and chronic infection (96.3%). The dominant HBV genotypes were C (68.9%) and B (28.4%). Among chronic HBV infection individuals, donors infected with HBV genotype B were older than those infected with genotype C (median age: 45y vs 38.5y, P<0.05). Additionally, they showed significantly lower HBsAg levels with a narrower distribution range than those infected with genotype C [median: 23.2 IU/mL (range: <0.05-7 910 IU/mL) vs 968 IU/mL (range: <0.05-3.4×10
), P<0.05]. However, no significant difference was observed in the HBV DNA loads between these two genotypes (P>0.05). Conclusion: Between 2013 and 2022, the prevalence of HBsAg among blood donors in Dalian showed a year-over-year decline. Chronic infection was predominant among HBsAg+ first-time blood donors. The characteristics of chronic infection in blood donors differed significantly depending on the viral genotype, manifesting as differences in age of infected individuals and HBsAg level distribution.
3.Factors affecting the prevalence of hyperuricemia in an island troop
Yongguang FANG ; Shujun SUN ; Chong TANG ; Chunyu LIU ; Qian XU ; Ying LIANG ; Huihui GUO ; Peng YANG ; Nannan CHEN
Journal of Navy Medicine 2025;46(6):574-578
Objective To analyze the factors affecting the prevalence of hyperuricemia(HUA)in an island troop.Methods A total of 1 113 soldiers stationed on an island from December 2021 to December 2022 were selected as research objects by cluster sampling.Their lifestyle and health information were collected.Physical examination and laboratory detection were conducted.Multivariate logistic regression was used to analyze the influencing factors of HUA.Results The prevalence rate of HUA was 21.02%(234/1 113).There were significant differences in the body mass index(BMI),waist-to-hip ratio,triglyceride,alanine aminotransferase,and creatinine between the soldiers with hyperuricemia and the soldiers with normal blood uric acid(P<0.05).Multivariate logistic regression analysis showed that BMI≥24(OR=1.49,95%CI:1.09-2.05),abnormal liver function(OR=2.26,95%CI:1.31-3.92),and dyslipidemia(OR=1.46,95%CI:1.01-2.12)were positively correlated with hyperuricemia;age>30 years old(OR=0.59,95%CI:0.37-0.93)and exercise time>1 h per week(OR=0.46,95%CI:0.22-0.97)were negatively correlated with HUA.Conclusion The prevalence rate of hyperuricemia is at a high level in an island troop.BMI≥24,age≤30 years old,exercise time≤1 h per week,abnormal liver function,and dyslipidemia are the risk factors for HUA.Prevention and control measures should be taken as early as possible for the soldiers with these risk factors.
4.Construction and validation of prediction models for delayed encephalopathy after acute carbon monoxide poisoning based on machine learning
Yanwu YU ; Yan ZHANG ; Ding YUAN ; Huihui HAO ; Fang YANG ; Hongyi YAN ; Pin JIANG ; Mengnan GUO ; Zhigao XU ; Changhua SUN ; Gaiqin YAN ; Lu CHE ; Jianjun GUO ; Jihong CHEN ; Yan LI ; Yanxia GAO
Chinese Journal of Emergency Medicine 2025;34(10):1403-1409
Objective:s To investigate the risk factors for delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) in patients with acute carbon monoxide poisoning (ACOP) and to develop predictive models based on machine learning algorithms.Methods:Patients with ACOP hospitalized at the First Affiliated Hospital of Zhengzhou University from August 2019 to October 2024 were included, with the occurrence of DEACMP as the outcome measure. The dataset was randomly divided into training and validation sets at a ratio of 7:3. Lasso regression was used to select features influencing the outcome in training sets. Nine machine learning models—including Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Support Vector Machine (SVM)—were constructed. Receiver operating characteristic (ROC) curves were plotted and the area under the curve (AUC) calculated for each model. Calibration curves were used to assess accuracy, and decision curve analysis (DCA) was applied to evaluate clinical utility. The SHapley Additive exPlanations (SHAP) method was employed to visualize and interpret the best-performing model.Results:A total of 264 ACOP patients were included, of whom 54 (20.5%) developed DEACMP. Lasso regression identified eight key feature variables. Based on these factors, predictive models were constructed, showing good AUC stability across the nine machine learning models in both training (0.92–0.99) and validation sets (0.85–0.91). The RF model performed best, with an AUC of 0.99 in the training set and 0.90 in the validation set; its calibration curve and DCA curve also demonstrated excellent performance. SHAP analysis of the RF model revealed the importance ranking of factors from highest to lowest as follows: Glasgow Coma Scale (GCS) score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, diastolic blood pressure (DBP), and drinking history.Conclusions:The RF model exhibited the highest predictive performance for DEACMP occurrence in ACOP patients. The influencing factors, ranked in order of importance from highest to lowest, are as follows: GCS score, duration of coma, age, history of coronary heart disease, CK-MB level, monocyte count, DBP, and drinking history.
5.The value of CEA, CYFRA21-1 and CA125 tests in opportunistic screening for non-small cell lung cancer: a meta-analysis
Honghai HE ; Huihui ZHANG ; Hua WU ; Hongli WANG ; Wei ZHAO ; Ping SUN ; Peng WANG
Chinese Journal of Health Management 2024;18(4):254-262
Objective:To evaluate the value of CEA, CYFRA21-1 and CA125 tests in opportunistic screening of non-small cell lung cancer (NSCLC) based on meta-analysis.Methods:The original research literatures on the diagnostic value of CEA, CYFRA21-1 and CA125 in Chinese NSCLC patients were searched from databases of PubMed, Embase, The Cochrane Library, CNKI, VIP, Database and Wanfang database from establishment to June 2023. The literature screening, data extraction and quality evaluation were carried out independently by two researchers. The quality evaluation tool of diagnostic accuracy studies was used to evaluate the quality of the literature. A summary receiver operating characteristic (SROC) curve was used to assess the overall effectiveness of the tests. The outcome stability and publication bias were detected by using sensitivity analysis and Deeks′ test.Results:A total of 23 studies met the inclusion and exclusion criteria were included. The results of meta-analysis showed that the overall sensitivity of CEA, CYFRA21-1 and CA125 alone in the diagnosis of NSCLC was relatively low, it was 0.49(95% CI: 0.43-0.55), 0.56(95% CI: 0.49-0.63) and 0.41(95% CI: 0.33-0.49), respectively. The overall sensitivity of the combined detection of the three markers for the diagnosis of NSCLC increased to 0.83(95% CI: 0.69-0.91), but the overall specificity decreased to 0.76(95% CI: 0.69-0.83). Conclusions:The single detection of CEA, CYFRA21-1 and CA125 is not recommended for screening NSCLC in population receiving physical examination. Although the sensitivity of the combined detection of CEA, CYFRA21-1 and CA125 for screening NSCLC is improved, but the specificity is decreased, the misdiagnosis rate is increased, so the screening effect is limited.
6.Single extract of Forsythia Suspense versus the prepared drug in pieces:comparison of their anti-inflammatory,antitumor and antibacterial effects in zebrafish
Xindeng GUO ; Zhuolin GUO ; Dongmei SUN ; Lifang ZOU ; Jinying OU ; Linzhong YU ; Zibin LU ; Huihui CAO ; Junshan LIU
Journal of Southern Medical University 2024;44(3):594-604
Objective To compare the anti-inflammatory,antitumor and anti-bacterial effects of the single extract(in granules)and the prepared drug in pieces of Forsythia Suspense(Lianqiao,a traditional Chinese herbal medicine).Methods In zebrafish embryo models of CuSO4 exposure,tail transection and LPS microinjection-induced inflammation,the anti-inflammatory effects of 10 μg/mL DEX,single extract of Forsythia Suspense,and the water extract of the prepared drug(400,600,and 800 μg/mL)were evaluated by observing neutrophil counts,RT-qPCR,HE staining and survival analysis.Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining.The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs.Results In the zebrafish embryo models of inflammation,both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation,reduced the mRNA expressions of TNF-α,IL-6,P38,Jnk,Erk and P65,and increased the survival rate of zebrafish.They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells(HCT116),pancreas adenocarcinoma cells(PANC-1),lung cancer cells(A549),liver cancer cells(Hep3B)and cervical carcinoma cells(Hela)in zebrafish embryos,and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL.Conclusion The two dosage forms of Forsythia Suspense have similar anti-inflammatory,antitumor and antibacterial effects,but their effects for inhibiting IL-6,P65,and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.
7.Effect of JCI standard-based management model on dispute prevention and its impact on patient satis-faction
Modern Hospital 2024;24(8):1235-1237
Objective To study the effectiveness of a management model based on the standards proposed by the Joint Commission on Accreditation of International Healthcare Organizations(JCI)in preventing disputes and investigate its impact on patient satisfaction.Methods A total of 102 patients between March 2022 to March 2024 were enrolled in the study.They were randomly divided into JCI standard group(n=51)and conventional group(n=51)using the random number method.The con-ventional group received the conventional management,while the JCI standard group followed the management based on the JCI standard.Occurrence of dispute events,patient satisfaction levels,management quality,and negative emotions before and after treatment were compared between the two groups.Results The total incidence of dispute events in JCI standard group was sig-nificantly lower than that in conventional group(1.96%vs 13.73%,P<0.05).The JCI standard group scored significantly higher in satisfactions with all items(all P<0.05)as well as in management quality(all P<0.05)compared to the convention-al group.Following treatment,negative emotion scores decreased in both groups compared to pre-treatment,with the JCI standard group showing significantly lower scores than the conventional group(all P<0.05).Conclusion Implementing the management model based on JCI standard notably can reduce the number of disputes,enhance patient satisfaction,improve management quali-ty,and alleviate negative emotions among patients.
8.Application of research-assisted teaching in Histology teaching——Taking the construction of rat spinal cord injury model as an example
Qi QI ; Weiyan ZOU ; Huihui LI ; Yanmei ZHOU ; Meiqun SUN
Journal of Shenyang Medical College 2024;26(3):316-320
Objective:To investigate the application effect of research-assisted teaching mode in histology teaching by taking the construction of rat spinal cord injury model as an example.Methods:A convenient sampling method was used to select 52 freshmen majoring in clinical medicine of grade 2020 in our school as the research subjects.They were randomly divided into the conventional teaching group and the research-assisted teaching group,with 26 students in each group.The conventional teaching group received traditional classroom teaching combined with experimental teaching.On this basis,research elements were added to the experimental teaching in the research-assisted teaching group to provide more in-depth research methods and experimental design,so as to cultivate students'research abilities.The theoretical assessment and practical skills assessment of histology course were compared between the two groups.A subjective evaluation questionnaire on experimental animal models teaching was used to evaluate the advantages of teaching programs in three dimensions:psychological quality training,technical skill enhancement,and theoretical knowledge expansion.The research abilities of the two groups were compared.Pearson correlation analysis was used to analyze the correlation between research ability scores and comprehensive scores.Results:The usual score and comprehensive score in the research-assisted teaching group were significantly higher than those in the conventional teaching group(P<0.05).The scores of adaptability to challenging tasks,determination and perseverance in problem-solving,communication skills in teamwork,literature reading,integration of practical experience with theoretical knowledge,practical application value of the course,and innovation of teaching resources in the research-assisted teaching group were higher than those in the conventional teaching group(P<0.05).The scores in experimental design ability,background knowledge in literature review,communication and reporting skills,awareness of evidence-based medicine,and overall research ability in the research-assisted teaching group were higher than those in the conventional teaching group(P<0.05).The total score of students'research abilities was positively correlated with comprehensive scores(r=0.716,P<0.01).Conclusions:The application of research-assisted teaching significantly improved students'research abilities in histology teaching.The enhancement of research abilities can promote the mastery of theoretical knowledge and the improvement of experimental skills.
9.Correlation between blood microRNA-133b and soluble FMS-like tyrosine kinase 1 levels and prognosis in patients with endometrial cancer
Huihui SUN ; Yanjuan GUO ; Nannan ZHAO ; Jianli ZHOU ; Jinling YUAN ; Jie GAO
Chongqing Medicine 2024;53(19):2943-2948
Objective To study the relationship between blood microRNA-133b(miR-133b)and solu-ble fms-like tyrosine kinase 1(sFLT1)levels with the prognosis in the patients with endometrial cancer.Methods A total of 122 patients with endometrial cancer visited in the gynecology department of this hospital from January 2015 to January 2016 were prospectively selected as the study subjects,and divided into the sur-vival group(n=58)and death group(n=64)according to the 5-year prognosis of the patients with endome-trial cancer.The miR-133b and sFLT1 levels were compared between the two groups.The COX regression was used to analyze the relationship between miR-133b and sFLT1 with the prognosis of the patients with en-dometrial cancer.Results The levels of miR-133b and sFLT1 in the survival group were higher than those in the death group,and the differences were statistically significant(P<0.05).The median survival time in the miR-133b low-level group was shorter than that in the miR-133b high level group,and the difference was sta-tistically significant(P<0.05).The median survival time of the sFLT1 low level group was shoeter than that in the sFLT1 high level group,and the difference was statistically significant(P<0.05).The FIGO stageⅢ-Ⅳ and lymph node metastasis were the independent risk factors for the prognosis of endometrial cancer(P<0.05),and the pathological G1-G2,high level of miR-133b and sFLT1 were the independent protective factors for the prognosis of endometrial cancer(P<0.05).Conclusion The miR-133b and sFLTl low levels in the patients with endometrial cancer are associated with the disease progression,and both are the independ-ent risk factors of prognosis.
10.Chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease:Correlations with blood eosinophil level
Lu YANG ; Yadan SHENG ; Kai YANG ; Liyu HE ; Huihui GU ; Guoqing SUN ; Weiting CHEN ; Bingjie ZHU ; Yanrong CHEN ; Chenwang JIN
Chinese Journal of Medical Imaging Technology 2024;40(8):1189-1193
Objective To observe the correlations of chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with blood eosinophil(EOS)level.Methods Chest CT data of 162 AECOPD patients with elevated eosinophils were retrospectively analyzed.The patients were divided into low EOS group(n=105)and high EOS group(n=57)according to the absolute counting of blood EOS.The quantitative CT parameters,including the number of whole lung bronchi and the volume of blood vessels,low-attenuation area percentage(LAA%)of whole lung,of left/right lung and each lobe of lung,as well as the luminal diameter(LD),wall thickness(WT),wall area(WA)and WA percentage of total bronchial cross-section(WA%)of grade 3 to 8 bronchi were compared between groups.Spearman correlations were performed to analyze the correlations of quantitative CT parameters with blood EOS level.Results LAA%of the whole lung,of the left/right lung and each lobe of lung,as well as of the upper lobe of right lung LDgrade4,middle lobe of right lung WTgrade5,upper lobe of right lung WAgrade4,middle lobe of right lung WAgrade5 and lower lobe of left lung WAgrade3 in low EOS group were all higher than those in high EOS group(all P<0.05).Except for the upper lobe of right lung LDgrade4,the above quantitative CT indexes being significant different between groups were all weakly and negatively correlated with blood EOS level(r=-0.335 to-0.164,all P<0.05).Conclusion Chest CT quantitative parameters of AECOPD patients were correlated with blood EOS level,among which LAA%,a part of WT and WA were all weakly negatively correlated with blood EOS level.

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