Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

N6-methyladenosine(m6A)modification is one of the most abundant epitranscriptomic modifications in eukaryotic mRNA,with dynamic and reversible properties.This modification process is coordinated by methyltransferases,demethylases,and related m6A binding proteins,which in turn affect mRNA metabolism and function.Increasing evi-dence has indicated that the m6A RNA modification plays an important role in the occurrence and development of athero-sclerosis(As)and other related diseases.This paper provide a comprehensive review of the relationship between m6A RNA modification and As.The entire manuscript summarizes the m6A RNA modification mechanism and its roles in As-related cells including endothelial cells,macrophages,and smooth muscle cells,and discusses the association of m6A RNA modification with risk factors of As such as high-fat diet,ischemia/hypoxia,oscillatory stress,and hypertension.Finally,this review summarizes researches on drug intervention targeting m6A RNA methylation to mitigate As.These studies pro-vide important references for exploring new targets for early diagnosis and treatment of As.

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE)followed by hepatic arterial infusion chemotherapy(HAIC)combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July,2020 and June,2023.23 of the patients received TACE combined with HAIC and TKI(TACE+HAIC+TKI group)and 47 received TACE combined with HAIC,PD-1 inhibitors and TKI(TACE+HAIC+PD-1+TKI group).The clinical characteristics,laboratory test results,efficacy,outcomes and adverse events of the patients were compared between the two groups.Results The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates(ORR;60.87%vs 36.17%,P=0.031),comparable disease control rates(95.65%vs 93.62%,P=0.068),and different median progression-free survival(PFS)time(10.2 vs 11.8 months,P=0.003)and median overall survival(OS)time(15.7 vs 19.5 months,P=0.035).After propensity score matching(PSM),the median PFS and OS time of the two groups was 10.1 vs 14.5 months(P=0.024)and 14.2 vs 21.2 months(P=0.221),respectively.The 1-year PFS rates of the 2 groups were 24.0%vs 52.2%,and the 1-,2-and 3-year OS rates were 72.3%vs 93.1%,23.9%vs 63.8%,and 23.9%vs 36.5%,respectively.The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group(21.28%vs 0,P=0.025),but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups.Conclusion The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

Objective:To explore the application of the semi-flipped classroom combined with knowledge point auction learning method in the theoretical teaching among stomatological students and its effectiveness.Methods:Undergraduates from four classes at Guanghua School of Stomatology, Sun Yat-Sen University were taken as research subjects. Students from two classes ( n=198) were taught using the semi-flipped classroom combined with the knowledge point auction learning method, while students from the other two classes ( n=172) were taught with the regular classroom teaching method as controls. Classroom quizzes were used to compare the two classes' mastery of important and difficult points, and a questionnaire was used to investigate students' feedback on the class outcomes. SPSS 22.0 was used for the independent samples t-test. Results:The mean test score of the experimental class was higher than that of the control class (88.51±11.02 vs. 80.40±8.53). The results of the questionnaire showed that students' interest in the course, comprehension and absorption of knowledge points, degree of satisfaction with the class, and mastery of the contents in sections in the experimental class were significantly higher than those in the control class (7.28±1.51 vs. 9.10±0.73, 6.92±1.44 vs. 8.69±1.62, 6.09±1.87 vs. 7.61±1.46, 6.40±1.04 vs. 7.70±0.86 ).Conclusions:The semi-flipped classroom combined with the knowledge point auction learning method is innovative and achieves good teaching outcomes. It holds promise for wider use in the theoretical teaching of various clinical subjects. To explore the application of the semi-flipped classroom combined with knowledge point auction learning method in the theoretical teaching among stomatological students and its effectiveness.

Objective To evaluate the efficacy and safety of transcatheter arterial chemoembolization(TACE)followed by hepatic arterial infusion chemotherapy(HAIC)combined with TKI drugs and PD-1 inhibitors as the first-line treatment for advanced hepatocellular carcinoma(HCC).Methods We retrospectively analyzed the data of 70 patients with advanced HCC treated in the Department of Oncology of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between July,2020 and June,2023.23 of the patients received TACE combined with HAIC and TKI(TACE+HAIC+TKI group)and 47 received TACE combined with HAIC,PD-1 inhibitors and TKI(TACE+HAIC+PD-1+TKI group).The clinical characteristics,laboratory test results,efficacy,outcomes and adverse events of the patients were compared between the two groups.Results The TACE+HAIC+TKI and TACE+HAIC+PD-1+TKI groups had significantly different objective remission rates(ORR;60.87%vs 36.17%,P=0.031),comparable disease control rates(95.65%vs 93.62%,P=0.068),and different median progression-free survival(PFS)time(10.2 vs 11.8 months,P=0.003)and median overall survival(OS)time(15.7 vs 19.5 months,P=0.035).After propensity score matching(PSM),the median PFS and OS time of the two groups was 10.1 vs 14.5 months(P=0.024)and 14.2 vs 21.2 months(P=0.221),respectively.The 1-year PFS rates of the 2 groups were 24.0%vs 52.2%,and the 1-,2-and 3-year OS rates were 72.3%vs 93.1%,23.9%vs 63.8%,and 23.9%vs 36.5%,respectively.The incidence of proteinuria was significantly higher in TACE+HAIC+PD-1+TKI group than in TACE+HAIC+TKI group(21.28%vs 0,P=0.025),but the incidences of grade 3-4 treatment-related adverse events were all similar between the two groups.Conclusion The first-line treatment with TACE+HAIC+PD-1+TKI is safe and effective for advanced HCC and can significantly prolong the survival of the patients.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine-glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

Objective:To investigate the status quo of preoperative decisional conflict in patients with traumatic amputation, analyze its influencing factors, and provide a reference for the development of targeted decision-making support programs.Methods:Totally 189 patients with traumatic amputation hospitalized in the Emergency Department of the First Affiliated Hospital of Zhengzhou University from January 2022 to October 2023 were selected by convenience sampling. Data were collected using a sociodemographic questionnaire, the Chinese version of the Decision Conflict Scale (DCS), the Control Preference Scale (CPS), and the Perceived Social Support Scale (PSSS). Data analysis was performed using SPSS 25.0.Results:A total of 196 questionnaires were distributed, with 189 valid responses, yielding an effective response rate of 96.4%. The average preoperative decisional conflict score among the 189 patients was (44.32 ± 9.27). During the decision-making process, 69 patients (36.5%) preferred a shared decision-making model, but 100 patients (52.9%) experienced a passive role. Multiple stepwise regression analysis indicated that the primary factors influencing decisional conflict were age, educational level, occupation, family income, actual participation role, family support (adjusted R2=0.799, P<0.01) . Conclusions:There is a discrepancy between the expected and actual participation roles in the decision-making process among patients with traumatic amputation, leading to a high level of preoperative decisional conflict. Several factors contribute to this conflict. Healthcare providers should pay particular attention to peasants, older patients, those with lower education and family income, respect patients' control preferences, and provide appropriate decision-making support.

Objective:To analyze the correlation between the degree of internal carotid artery tortuosity and plaque burden through dual-source computed tomography (CT),and to further investigate the relationship between the internal carotid artery tortuosity and the formation of cerebral infarction. Methods:A total of 106 patients with internal carotid artery tortuosity,who underwent computed tomography angiography (CTA) examination on head and neck at the First People's Hospital of Lianyungang from December 2021 to December 2022,were retrospectively selected. The patients were divided into a cerebral infarction group and a non-cerebral infarction group based on cranial magnetic resonance imaging (MRI) examination,with 53 cases in each group. The internal carotid artery tortuosity-related indicators (tortuosity index,degree of vascular deviation,vascular tortuosity),and the parameters of plaque characteristic (plaque area,vascular area and plaque burden) between the two groups were compared. Univariate and multivariate analyses were used,and the information of age,gender,history of underlying disease (such as hypertension,diabetes,coronary heart disease,etc.),lifestyle habits (such as smoking,drinking),and stroke history of patients in both groups were collected. Clinical biochemical indicators included triglycerides,total cholesterol,low-density lipoprotein,high-density lipoprotein,lipoprotein a,and homocysteine. Independent risk factors of affecting plaque burden and cerebral infarction were explored. Pearson correlation analysis was used to examine the correlation between the indicators of internal carotid artery tortuosity and plaque burden of the patients,as well as the relationship between the carotid artery tortuosity and the formation of cerebral infarction. The receiver operating characteristic (ROC) curve was used to assess the predictive ability of indicators of patients for cerebral infarction. Results:The index of internal carotid artery tortuosity,degree of vascular deviation,plaque burden,plaque area,and degree of carotid artery stenosis were significantly positively correlated with cerebral infarction (r=0.310,0.203,0.345,0.320,0.292,P<0.05),respectively. ROC curve analysis showed that the area under curve (AUC) values of tortuosity index and plaque burden were respectively 0.679 and 0.677 in predicting cerebral infarction. The AUC value of combined indicator (tortuosity index+plaque burden) was 0.806 in predicting cerebral infarction,which was significantly higher than that of single indicator that was singly used (95％CI:0.722-0.89,P<0.01). Conclusion:There are significant correlation between the degree of internal carotid artery tortuosity,plaque burden,and formation of cerebral infarction. The combined use of the tortuosity index and plaque burden can significantly improve the predictive accuracy for cerebral infarction.

Objective:To analyze the correlation between the degree of internal carotid artery tortuosity and plaque burden through dual-source computed tomography (CT),and to further investigate the relationship between the internal carotid artery tortuosity and the formation of cerebral infarction. Methods:A total of 106 patients with internal carotid artery tortuosity,who underwent computed tomography angiography (CTA) examination on head and neck at the First People's Hospital of Lianyungang from December 2021 to December 2022,were retrospectively selected. The patients were divided into a cerebral infarction group and a non-cerebral infarction group based on cranial magnetic resonance imaging (MRI) examination,with 53 cases in each group. The internal carotid artery tortuosity-related indicators (tortuosity index,degree of vascular deviation,vascular tortuosity),and the parameters of plaque characteristic (plaque area,vascular area and plaque burden) between the two groups were compared. Univariate and multivariate analyses were used,and the information of age,gender,history of underlying disease (such as hypertension,diabetes,coronary heart disease,etc.),lifestyle habits (such as smoking,drinking),and stroke history of patients in both groups were collected. Clinical biochemical indicators included triglycerides,total cholesterol,low-density lipoprotein,high-density lipoprotein,lipoprotein a,and homocysteine. Independent risk factors of affecting plaque burden and cerebral infarction were explored. Pearson correlation analysis was used to examine the correlation between the indicators of internal carotid artery tortuosity and plaque burden of the patients,as well as the relationship between the carotid artery tortuosity and the formation of cerebral infarction. The receiver operating characteristic (ROC) curve was used to assess the predictive ability of indicators of patients for cerebral infarction. Results:The index of internal carotid artery tortuosity,degree of vascular deviation,plaque burden,plaque area,and degree of carotid artery stenosis were significantly positively correlated with cerebral infarction (r=0.310,0.203,0.345,0.320,0.292,P<0.05),respectively. ROC curve analysis showed that the area under curve (AUC) values of tortuosity index and plaque burden were respectively 0.679 and 0.677 in predicting cerebral infarction. The AUC value of combined indicator (tortuosity index+plaque burden) was 0.806 in predicting cerebral infarction,which was significantly higher than that of single indicator that was singly used (95％CI:0.722-0.89,P<0.01). Conclusion:There are significant correlation between the degree of internal carotid artery tortuosity,plaque burden,and formation of cerebral infarction. The combined use of the tortuosity index and plaque burden can significantly improve the predictive accuracy for cerebral infarction.

Objective:To investigate the status quo of preoperative decisional conflict in patients with traumatic amputation, analyze its influencing factors, and provide a reference for the development of targeted decision-making support programs.Methods:Totally 189 patients with traumatic amputation hospitalized in the Emergency Department of the First Affiliated Hospital of Zhengzhou University from January 2022 to October 2023 were selected by convenience sampling. Data were collected using a sociodemographic questionnaire, the Chinese version of the Decision Conflict Scale (DCS), the Control Preference Scale (CPS), and the Perceived Social Support Scale (PSSS). Data analysis was performed using SPSS 25.0.Results:A total of 196 questionnaires were distributed, with 189 valid responses, yielding an effective response rate of 96.4%. The average preoperative decisional conflict score among the 189 patients was (44.32 ± 9.27). During the decision-making process, 69 patients (36.5%) preferred a shared decision-making model, but 100 patients (52.9%) experienced a passive role. Multiple stepwise regression analysis indicated that the primary factors influencing decisional conflict were age, educational level, occupation, family income, actual participation role, family support (adjusted R2=0.799, P<0.01) . Conclusions:There is a discrepancy between the expected and actual participation roles in the decision-making process among patients with traumatic amputation, leading to a high level of preoperative decisional conflict. Several factors contribute to this conflict. Healthcare providers should pay particular attention to peasants, older patients, those with lower education and family income, respect patients' control preferences, and provide appropriate decision-making support.