1.Pristimerin induces Noxa-dependent apoptosis by activating the FoxO3a pathway in esophageal squamous cell carcinoma.
Mengyuan FENG ; Anjie ZHANG ; Jingyi WU ; Xinran CHENG ; Qingyu YANG ; Yunlai GONG ; Xiaohui HU ; Wentao JI ; Xianjun YU ; Qun ZHAO
Chinese Journal of Natural Medicines (English Ed.) 2025;23(5):585-592
Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics*
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Humans
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Apoptosis/drug effects*
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Esophageal Squamous Cell Carcinoma/physiopathology*
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Esophageal Neoplasms/physiopathology*
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Pentacyclic Triterpenes
;
Animals
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Cell Line, Tumor
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Proto-Oncogene Proteins c-bcl-2/genetics*
;
Mice
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Signal Transduction/drug effects*
;
Mice, Nude
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Cell Proliferation/drug effects*
;
Triterpenes/pharmacology*
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Xenograft Model Antitumor Assays
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Mice, Inbred BALB C
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Male
;
Gene Expression Regulation, Neoplastic/drug effects*
2.Analysis on epidemiological characteristics of influenza and genetic characteristics of influenza virus in 2023-2024 surveillance year in Shandong Province
Yujie HE ; Lin SUN ; Shaoxia SONG ; Shu ZHANG ; Julong WU ; Yang DONG ; Zhong LI ; Xianjun WANG ; Zengqiang KOU ; Ti LIU
Chinese Journal of Epidemiology 2025;46(3):430-439
Objective:To analyze the epidemiological, etiological and genetic characteristics of influenza virus in Shandong Province during 2023-2024.Methods:The surveillance data of influenza-like illness (ILI) in sentinel hospitals in Shandong from 2023 to 2024 were collected and analyzed. The isolated influenza strains with hemagglutination titers ≥8 were selected for antigenicity analysis, drug susceptibility test, gene sequencing and evolutionary analysis.Results:From 2023 to 2024, the positive rate of influenza virus in Shandong was 8.51% (23 663/277 995), the highest positive rate was in the age group of 5-14 years (15.78%, 6 073/38 478), and the highest positive rate was in the 49 th week (35.86%, 2 264/6 313). Both antigenicity analysis and evolutionary analysis showed that the A(H1N1)pdm09 subtype and B(Victoria) strain had good matching effect and close evolutionary distance with the 2023-2024 surveillance year vaccine strain. The A(H3N2) subtype strain did not have a high matching effect with the 2023-2024 vaccine strain and had a long evolutionary distance, but had a close evolutionary distance with the 2024-2025 vaccine strain. Drug susceptibility test showed that oseltamivir sensitivity of influenza A(H1N1)pdm09 strain decreased greatly, and the amino acid site mutation of neuraminidase was H275Y. Conclusions:In the 2023-2024 surveillance year, the peak of influenza virus epidemic in Shandong was mainly occurred in winter and spring, and the age group of 5-14 years was the focus of prevention and control. The dominant strain was subtype A(H3N2), which had poor matching effect with the vaccine strain in the 2023-2024 surveillance year. One A(H1N1)pdm09 resistant strain was found in the drug resistance monitoring work. Follow-up prevention and control work should be strengthen the surveillance for the epidemiological characteristics, genetic variation and drug resistance of influenza viruses, timely understand the epidemic trend and mutation of influenza viruses, timely discover drug-resistant strains of influenza viruses, promote influenza vaccination, and improve of influenza prevention and control.
3.Analysis of the nucleic acid detection results for six non-influenza viruses in influenza-like illness cases in Shandong Province from 2020 to 2021
Yujie HE ; Zhong LI ; Julong WU ; Lin SUN ; Shaoxia SONG ; Shu ZHANG ; Xiaolin LIU ; Yang DONG ; Xianjun WANG ; Zengqiang KOU ; Ti LIU
Chinese Journal of Preventive Medicine 2025;59(2):216-221
Objective:To analyze the respiratory virus infection status and epidemiological characteristics of influenza-like illness (ILI) cases in Shandong Province during the 2020 -2021 influenza surveillance year. Methods:According to the National Influenza Surveillance Plan (2017 version), throat swab samples of ILI cases were collected from 14 surveillance sentinel hospitals in Shandong Province. Nucleic acid was extracted from all samples. Real-time fluorescence quantitative PCR (RT-PCR) was utilized to detect six common viruses, including human metapneumovirus (HMPV), human parainfluenza virus (HPIV) types 1, 2 and 3, respiratory syncytial virus (RSV), and adenovirus (ADV). Subsequently, the obtained detection results were analyzed.Results:A total of 2 386 specimens were collected, with a detection rate of 24.22% (578). Six viruses were detected, with detection rates of 6.75% (162 cases) for HMPV, 5.87% (140 cases) for RSV, 3.56% (85 cases) for HPIV3, 3.14% (75 cases) for HPIV2, 2.98% (71 cases) for HPIV1, and 2.77% (66 cases) for ADV. There was no significant difference in detection rates between genders, but a notable variation among different age groups ( P<0.001). The highest detection rate was observed in individuals aged 0-4 years (31.94%), followed by those aged≥60 years (26.06%). The prevalence of six viruses showed a monthly variation, with the detection rate of HMPV being higher in December and HPIV1 being higher in February. HPIV2, HPIV3, RSV, and ADV had higher detection rates in November. The co-detection rate of multiple viruses was 0.80%, with RSV being the most common pathogen involved in co-detection, primarily in individuals aged 0-4 years. Conclusion:The detection of six multiple pathogens in ILI cases in Shandong Province is dominated by HMPV, RSV and HPIV3. The prevalence of respiratory viruses varies by age and time.
4.Early endovascular treatment for cerebral infarction caused by intracranial atherosclerosis or cardioembolism:a comparative study
Youqing XU ; Haichen SHEN ; Xiangjun XU ; Junfeng XU ; Ke YANG ; Xianhui DING ; Xianjun HUANG
Journal of Interventional Radiology 2025;34(9):931-934
Objective To compare the clinical efficacy and safety of early endovascular treatment(EVT)for the stroke patients caused by large vessel occlusion(LVO)due to intracranial atherosclerosis(ICAS)or due to cardioembolism(CE).Methods The clinical data of 488 patients with acute anterior circulation LVO stroke,who received early endovascular treatment at the Yijishan Hospital of Wannan Medical College of China from October 2015 to December 2023,were retrospectively analyzed.According to the cause of disease,the patients were divided into ICAS group(n=108)and CE group(n=380).The clinical data,mainly including the proportion of patients having a good prognosis at 90 days after operation(modified Rankin Scale score ≤2 points),the incidence of symptomatic intracranial cerebral hemorrhage(sICH),and the mortality of patients at 90 days after operation.Multivariate logistic regression analysis was used to analyze the factors influencing patient's prognosis.Results Of the 488 patients,29(5.9%)developed postoperative sICH,242(49.6%)achieved a good prognosis at 90 days after the operation,and 91(18.6%)died.The above outcomes in the ICAS group were one,66,and 11 patients respectively,which in the CE group were 28,176,and 80 respectively,and the differences between the two groups were statistically significant(all P<0.05).Multivariate logistic regression analysis indicated that good prognosis at 90 days after the operation(OR=0.962,95%CI:0.404-2.288,P=0.930)and the postoperative 90-day mortality(OR=1.379,95%CI:0.436-4.362,P=0.584)were not the factors influencing prognosis,while the postoperative sICH(OR=19.132,95%CI:1.332-274.791,P=0.030)was the factor influencing prognosis.Conclusion In CE group,the incidence of sICH and the postoperative 90-day mortality are higher,while in ICAS group,the postoperative 90-day good prognosis rate is higher.The postoperative sICH is the factor influencing prognosis.
5.Construction of a Disease-Syndrome Integrated Diagnosis and Treatment System for Gastric "Inflammation-Cancer" Transformation Based on Multi-Modal Phenotypic Modeling
Hao LI ; Huiyao ZHANG ; Wei BAI ; Tingting ZHOU ; Guodong HUANG ; Xianjun RAO ; Yang YANG ; Lijun BAI ; Wei WEI
Journal of Traditional Chinese Medicine 2025;66(5):458-463
By analyzing the current application of multi-modal data in the diagnosis of gastric "inflammation-cancer" transformation, this study explored the feasibility and strategies for constructing a disease-syndrome integrated diagnosis and treatment system. Based on traditional Chinese medicine (TCM) phenomics, we proposed utilizing multi-modal data from literature research, cross-sectional studies, and cohort follow-ups, combined with artificial intelligence technology, to establish a multi-dimensional diagnostic and treatment index system. This approach aims to uncover the complex pathogenesis and transformation patterns of gastric "inflammation-cancer" progression. Additionally, by dynamically collecting TCM four-diagnostic information and modern medical diagnostic information through a long-term follow-up system, we developed three major modules including information extraction, multi-modal phenotypic modeling, and information output, to make it enable real-world clinical data-driven long-term follow-up and treatment of chronic atrophic gastritis. This system can provide technical support for clinical diagnosis, treatment evaluation, and research, while also offering insights and methods for intelligent TCM diagnosis.
6.Analysis of the influencing factors of early neurological deterioration and short-term prognosis in minor acute ischemic stroke patients
Longsheng CHU ; Xianjun HUANG ; Chenglei WANG ; Bohao WEI ; Yuepei GAO ; Ameng LI ; Ke YANG ; Junfeng XU ; Xianjin SHANG ; Zhiming ZHOU
Chinese Journal of Cerebrovascular Diseases 2025;22(8):524-536
Objective To investigate the influencing factors associated with early neurological deterioration(END)in patients with minor acute ischemic stroke(mAIS),develop a clinical prediction model for END,and identify independent risk factors for 90-day neurological functional outcomes after stroke.Methods mAIS patients admitted consecutively to the Department of Neurology,Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College),from July 2023 to July 2024 were retrospectively collected.A minor ischemic stroke was defined as acute ischemic stroke with a National Institutes of Health stroke scale(NIHSS)score≤5 on admission.Baseline,clinical,and imaging data of all mAIS patients were collected and recorded,including demographic information(age,sex),past medical history(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,alcohol consumption,baseline blood pressure,pre-onset modified Rankin scale(mRS),NIHSS scores at admission and during hospitalization(24 hours,48 hours,72 hours after admission),motor component subscore of the NIHSS scores,NIHSS scores at discharge,trial of Org 10172 in acute stroke treatment(TOAST)classification,laboratory indicators(fasting blood glucose,hemoglobin A1c[HbA1c],total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein),clinical treatment information(intravenous thrombolysis,mono antiplatelet therapy,dual antiplatelet therapy,anticoagulation therapy)and length of stay.The status of stenosis and occlusion in the culprit vessel were assessed based on imaging results.Mild-to-moderate stenosis was defined as a stenosis rate of 0%to 69%,severe stenosis as a stenosis rate of 70%to 99%,and occlusion as complete interruption of the supplying artery.END was defined as an increase in NIHSS score of ≥2 points from baseline within 72 hours after admission,combined with an increase of at least 1 point in the motor score compared to the score at admission.Prognosis was assessed via telephone follow-ups at 90-day after onset using mRS score,with an mRS score ≤ 2 indicating a favorable outcome and an mRS score>2 indicating a poor outcome.Variables with P<0.05 in the univariate analysis were incorporated into multivariate Logistic regression analysis to identify the independent risk factors for END in mAIS patients.A nomogram model was constructed,and calibration curves along with decision curve analysis were plotted to evaluate the model's goodness-of-fit and clinical utility.Univariate and multivariate Logistic regression analyses were performed to identify factors associated with poor 90-day functional outcome after mAIS.Results(1)A total of 826 patients were included,aged 33-94 years,with a median age of 67(57,76)years.There were 571 males and 255 females.The NIHSS score at admission ranged from 0 to 5,with a median NIHSS score at admission of 3(2,4).The NIHSS motor subscore at admission ranged from 0 to 5,with a median baseline NIHSS motor score of 2(0,2).Among them,119 patients(14.4%)were in the END group and 707 patients(85.6%)were included in the non-END group.At 90days after stroke,744 patients(90.1%)had a favorable outcome,while 82 patients(9.9%)had a poor outcome.(2)Univariate analysis showed that there were statistically significant differences between the END group and the non-END group in terms of HbA1c,fasting blood glucose,baseline NIHSS score,baseline NIHSS motor subscore,history of alcohol consumption,diabetes mellitus,culprit vessel stenosis and occlusion,and TOAST classification(all P<0.05).Statistically significant differences were observed between the favorable outcome group and the poor outcome group in HbA1c,fasting blood glucose,incidence of END,baseline NIHSS score,discharge NIHSS score,culprit vessel stenosis and occlusion,TOAST classification,and history of alcohol consumption(all P<0.05).(3)Multivariate Logistic regression analysis indicated that mAIS patients with severe stenosis of the culprit vessel(OR,5.88,95%CI2.32-14.91,P<0.01),occlusion of the culprit vessel(OR,5.74,95%CI 2.25-14.62,P<0.01),history of alcohol consumption(OR,5.59,95%CI3.41-9.17,P<0.01),elevated HbA1c(OR,1.67,95%CI 1.35-2.08,P<0.01),and higher baseline NIHSS motor score(OR,1.43,95%CI 1.08-1.89,P=0.012)had an increased risk of END.A higher discharge NIHSS score(OR,2.59,95%CI 1.89-3.57,P<0.01)and the occurrence of END(OR,18.42,95%CI 5.13-66.18,P<0.01)were associated with poor 90-day functional outcome after mAIS.(4)The nomogram model constructed based on independent risk factors of END in mAIS patients demonstrated an AUC of 0.78(95%CI 0.73-0.83)for predicting END,with a sensitivity of 0.8 and a specificity of 0.7.The model showed good calibration,and the Hosmer-Lemeshow test indicated good agreement between predicted and observed values(P=0.333).Decision curve analysis revealed that the model provided a high net benefit across a range of high-risk thresholds(0.1-0.7),suggesting its potential clinical utility.Conclusions Severe stenosis of the culprit vessel,occlusion of the culprit vessel,glycated hemoglobin levels,baseline NIHSS motor subscale scores,and history of alcohol consumption are independent risk factors for END in patients with mAIS.The nomogram model constructed based on these factors demonstrated good predictive performance.END and NIHSS scores at discharge are independent predictors of poor 90-day outcomes in patients with mAIS.
7.Analysis on epidemiological characteristics of influenza and genetic characteristics of influenza virus in 2023-2024 surveillance year in Shandong Province
Yujie HE ; Lin SUN ; Shaoxia SONG ; Shu ZHANG ; Julong WU ; Yang DONG ; Zhong LI ; Xianjun WANG ; Zengqiang KOU ; Ti LIU
Chinese Journal of Epidemiology 2025;46(3):430-439
Objective:To analyze the epidemiological, etiological and genetic characteristics of influenza virus in Shandong Province during 2023-2024.Methods:The surveillance data of influenza-like illness (ILI) in sentinel hospitals in Shandong from 2023 to 2024 were collected and analyzed. The isolated influenza strains with hemagglutination titers ≥8 were selected for antigenicity analysis, drug susceptibility test, gene sequencing and evolutionary analysis.Results:From 2023 to 2024, the positive rate of influenza virus in Shandong was 8.51% (23 663/277 995), the highest positive rate was in the age group of 5-14 years (15.78%, 6 073/38 478), and the highest positive rate was in the 49 th week (35.86%, 2 264/6 313). Both antigenicity analysis and evolutionary analysis showed that the A(H1N1)pdm09 subtype and B(Victoria) strain had good matching effect and close evolutionary distance with the 2023-2024 surveillance year vaccine strain. The A(H3N2) subtype strain did not have a high matching effect with the 2023-2024 vaccine strain and had a long evolutionary distance, but had a close evolutionary distance with the 2024-2025 vaccine strain. Drug susceptibility test showed that oseltamivir sensitivity of influenza A(H1N1)pdm09 strain decreased greatly, and the amino acid site mutation of neuraminidase was H275Y. Conclusions:In the 2023-2024 surveillance year, the peak of influenza virus epidemic in Shandong was mainly occurred in winter and spring, and the age group of 5-14 years was the focus of prevention and control. The dominant strain was subtype A(H3N2), which had poor matching effect with the vaccine strain in the 2023-2024 surveillance year. One A(H1N1)pdm09 resistant strain was found in the drug resistance monitoring work. Follow-up prevention and control work should be strengthen the surveillance for the epidemiological characteristics, genetic variation and drug resistance of influenza viruses, timely understand the epidemic trend and mutation of influenza viruses, timely discover drug-resistant strains of influenza viruses, promote influenza vaccination, and improve of influenza prevention and control.
8.Analysis of the nucleic acid detection results for six non-influenza viruses in influenza-like illness cases in Shandong Province from 2020 to 2021
Yujie HE ; Zhong LI ; Julong WU ; Lin SUN ; Shaoxia SONG ; Shu ZHANG ; Xiaolin LIU ; Yang DONG ; Xianjun WANG ; Zengqiang KOU ; Ti LIU
Chinese Journal of Preventive Medicine 2025;59(2):216-221
Objective:To analyze the respiratory virus infection status and epidemiological characteristics of influenza-like illness (ILI) cases in Shandong Province during the 2020 -2021 influenza surveillance year. Methods:According to the National Influenza Surveillance Plan (2017 version), throat swab samples of ILI cases were collected from 14 surveillance sentinel hospitals in Shandong Province. Nucleic acid was extracted from all samples. Real-time fluorescence quantitative PCR (RT-PCR) was utilized to detect six common viruses, including human metapneumovirus (HMPV), human parainfluenza virus (HPIV) types 1, 2 and 3, respiratory syncytial virus (RSV), and adenovirus (ADV). Subsequently, the obtained detection results were analyzed.Results:A total of 2 386 specimens were collected, with a detection rate of 24.22% (578). Six viruses were detected, with detection rates of 6.75% (162 cases) for HMPV, 5.87% (140 cases) for RSV, 3.56% (85 cases) for HPIV3, 3.14% (75 cases) for HPIV2, 2.98% (71 cases) for HPIV1, and 2.77% (66 cases) for ADV. There was no significant difference in detection rates between genders, but a notable variation among different age groups ( P<0.001). The highest detection rate was observed in individuals aged 0-4 years (31.94%), followed by those aged≥60 years (26.06%). The prevalence of six viruses showed a monthly variation, with the detection rate of HMPV being higher in December and HPIV1 being higher in February. HPIV2, HPIV3, RSV, and ADV had higher detection rates in November. The co-detection rate of multiple viruses was 0.80%, with RSV being the most common pathogen involved in co-detection, primarily in individuals aged 0-4 years. Conclusion:The detection of six multiple pathogens in ILI cases in Shandong Province is dominated by HMPV, RSV and HPIV3. The prevalence of respiratory viruses varies by age and time.
9.Analysis of the influencing factors of early neurological deterioration and short-term prognosis in minor acute ischemic stroke patients
Longsheng CHU ; Xianjun HUANG ; Chenglei WANG ; Bohao WEI ; Yuepei GAO ; Ameng LI ; Ke YANG ; Junfeng XU ; Xianjin SHANG ; Zhiming ZHOU
Chinese Journal of Cerebrovascular Diseases 2025;22(8):524-536
Objective To investigate the influencing factors associated with early neurological deterioration(END)in patients with minor acute ischemic stroke(mAIS),develop a clinical prediction model for END,and identify independent risk factors for 90-day neurological functional outcomes after stroke.Methods mAIS patients admitted consecutively to the Department of Neurology,Yijishan Hospital of Wannan Medical College(the First Affiliated Hospital of Wannan Medical College),from July 2023 to July 2024 were retrospectively collected.A minor ischemic stroke was defined as acute ischemic stroke with a National Institutes of Health stroke scale(NIHSS)score≤5 on admission.Baseline,clinical,and imaging data of all mAIS patients were collected and recorded,including demographic information(age,sex),past medical history(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation),smoking history,alcohol consumption,baseline blood pressure,pre-onset modified Rankin scale(mRS),NIHSS scores at admission and during hospitalization(24 hours,48 hours,72 hours after admission),motor component subscore of the NIHSS scores,NIHSS scores at discharge,trial of Org 10172 in acute stroke treatment(TOAST)classification,laboratory indicators(fasting blood glucose,hemoglobin A1c[HbA1c],total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein),clinical treatment information(intravenous thrombolysis,mono antiplatelet therapy,dual antiplatelet therapy,anticoagulation therapy)and length of stay.The status of stenosis and occlusion in the culprit vessel were assessed based on imaging results.Mild-to-moderate stenosis was defined as a stenosis rate of 0%to 69%,severe stenosis as a stenosis rate of 70%to 99%,and occlusion as complete interruption of the supplying artery.END was defined as an increase in NIHSS score of ≥2 points from baseline within 72 hours after admission,combined with an increase of at least 1 point in the motor score compared to the score at admission.Prognosis was assessed via telephone follow-ups at 90-day after onset using mRS score,with an mRS score ≤ 2 indicating a favorable outcome and an mRS score>2 indicating a poor outcome.Variables with P<0.05 in the univariate analysis were incorporated into multivariate Logistic regression analysis to identify the independent risk factors for END in mAIS patients.A nomogram model was constructed,and calibration curves along with decision curve analysis were plotted to evaluate the model's goodness-of-fit and clinical utility.Univariate and multivariate Logistic regression analyses were performed to identify factors associated with poor 90-day functional outcome after mAIS.Results(1)A total of 826 patients were included,aged 33-94 years,with a median age of 67(57,76)years.There were 571 males and 255 females.The NIHSS score at admission ranged from 0 to 5,with a median NIHSS score at admission of 3(2,4).The NIHSS motor subscore at admission ranged from 0 to 5,with a median baseline NIHSS motor score of 2(0,2).Among them,119 patients(14.4%)were in the END group and 707 patients(85.6%)were included in the non-END group.At 90days after stroke,744 patients(90.1%)had a favorable outcome,while 82 patients(9.9%)had a poor outcome.(2)Univariate analysis showed that there were statistically significant differences between the END group and the non-END group in terms of HbA1c,fasting blood glucose,baseline NIHSS score,baseline NIHSS motor subscore,history of alcohol consumption,diabetes mellitus,culprit vessel stenosis and occlusion,and TOAST classification(all P<0.05).Statistically significant differences were observed between the favorable outcome group and the poor outcome group in HbA1c,fasting blood glucose,incidence of END,baseline NIHSS score,discharge NIHSS score,culprit vessel stenosis and occlusion,TOAST classification,and history of alcohol consumption(all P<0.05).(3)Multivariate Logistic regression analysis indicated that mAIS patients with severe stenosis of the culprit vessel(OR,5.88,95%CI2.32-14.91,P<0.01),occlusion of the culprit vessel(OR,5.74,95%CI 2.25-14.62,P<0.01),history of alcohol consumption(OR,5.59,95%CI3.41-9.17,P<0.01),elevated HbA1c(OR,1.67,95%CI 1.35-2.08,P<0.01),and higher baseline NIHSS motor score(OR,1.43,95%CI 1.08-1.89,P=0.012)had an increased risk of END.A higher discharge NIHSS score(OR,2.59,95%CI 1.89-3.57,P<0.01)and the occurrence of END(OR,18.42,95%CI 5.13-66.18,P<0.01)were associated with poor 90-day functional outcome after mAIS.(4)The nomogram model constructed based on independent risk factors of END in mAIS patients demonstrated an AUC of 0.78(95%CI 0.73-0.83)for predicting END,with a sensitivity of 0.8 and a specificity of 0.7.The model showed good calibration,and the Hosmer-Lemeshow test indicated good agreement between predicted and observed values(P=0.333).Decision curve analysis revealed that the model provided a high net benefit across a range of high-risk thresholds(0.1-0.7),suggesting its potential clinical utility.Conclusions Severe stenosis of the culprit vessel,occlusion of the culprit vessel,glycated hemoglobin levels,baseline NIHSS motor subscale scores,and history of alcohol consumption are independent risk factors for END in patients with mAIS.The nomogram model constructed based on these factors demonstrated good predictive performance.END and NIHSS scores at discharge are independent predictors of poor 90-day outcomes in patients with mAIS.
10.Effect of FCN gene single nucleotide polymorphism on the susceptibility of pre-eclampsia in Han nationality pregnant women
Jiayu TAN ; Yuling TAN ; Bo YANG ; Wei YANG ; Chunlei YUAN ; Xianjun MI ; Feng′e CAI ; Yujie GAN ; Yanjun HE
Chinese Journal of Obstetrics and Gynecology 2024;59(11):839-847
Objective:To investigate the effect of single nucleotide polymorphism (SNP) of FCN gene on the susceptibility of pre-eclampsia (PE) in Han nationality pregnant women.Methods:A total of 274 PE pregnant women (PE group) and 154 healthy pregnant women (control group) admitted to Boai Hospital of Zhongshan, Affiliated Hospital to Southern Medical University from October 2020 to October 2022 were collected. The general information, medical history, reproductive history, blood pressure, body mass index and blood biochemical indicators before delivery were compared between the two groups. Twenty-three SNP loci of FCN gene family were genotyped by time-of-flight mass spectrometry, and the serum levels of ficolins (ficolin-1, -2 and -3) were detected by enzyme-linked immunosorbent assay.Results:(1) Compared with the control group, the body mass index, mean arterial pressure, gestational age at delivery, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, direct bilirubin, albumin, and C-reactive protein in the PE group were significantly higher than those in the control group (all P<0.05). The levels of N-terminal pro-B type natriuretic peptide (NT-proBNP), placental growth factor (PlGF) and human soluble vascular endothelial growth factor receptor-1 (sFlt-1) were significantly different between the two groups (all P<0.05). (2) Among the 23 SNP loci in FCN gene family, 18 loci were in Hardy-Weinberg genetic equilibrium, including 5 loci in FCN1 gene, 10 loci in FCN2 gene, and 3 loci in FCN3 gene. Five loci that did not conform to Hardy-Weinberg genetic equilibrium were not included in the subsequent analysis. Compared with the control group, the genotype distribution of 3 loci of FCN2 gene (rs7872508, rs11103563, rs73664188) and 1 locus of FCN3 gene (rs3813800) in the PE group were significantly different (all P<0.05). After Bonferroni correction, only the genotype distribution of rs7872508 and rs73664188 in FCN2 gene were statistically different between the PE group and the control group (all P<0.05). Further analysis showed that for the rs7872508 locus of FCN2 gene, compared with GG genotype, genotype GT ( OR=3.025, 95% CI: 1.080-8.471) and TT ( OR=4.777, 95% CI: 1.758-12.979) both significantly increased the risk of PE (both P<0.05). For rs73664188 locus of FCN2 gene, compared with TT genotype, genotype TC ( OR=0.510, 95% CI: 0.334-0.778) significantly reduced the risk of PE ( P<0.05). (3) Compared with the control group, the serum levels of ficolin-1 and ficolin-2 in pregnant women in the PE group were significantly reduced (both P<0.05), while the level of ficolin-3 showed no significant change ( P=0.271). Correlation analysis showed that the serum levels of ficolin-2 in pregnant women in the PE group were significantly positively correlated with PlGF level ( r=0.321, P<0.001), and significantly negatively correlated with sFlt-1 level ( r=-0.187, P=0.002) and NT-proBNP level ( r=-0.392, P<0.001). Further analysis revealed that the serum levels of ficolin-2 in pregnant women of the PE group with GT and TT genotypes at rs7872508 locus of FCN2 gene were significantly reduced (both P<0.05), while the serum level of ficolin-2 in pregnant women of the PE group with TC genotype at the rs73664188 locus were significantly increased ( P<0.05). Conclusion:The SNP of FCN2 gene in FCN gene family might be related to the susceptibility to PE and have an effect on serum ficolin-2 level in PE pregnant women.

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