Background:Missing data are frequently occurred in clinical studies.Due to the development of precision medicine,there is an increased interest in N-of-1 trial.Bayesian models are one of main statistical methods for a...Background:Missing data are frequently occurred in clinical studies.Due to the development of precision medicine,there is an increased interest in N-of-1 trial.Bayesian models are one of main statistical methods for analyzing the data of N-of-1 trials.This simulation study aimed to compare two statistical methods for handling missing values of quantitative data in Bayesian N-of-1 trials.Methods:The simulated data of N-of-1 trials with different coefficients of autocorrelation,effect sizes and missing ratios are obtained by SAS 9.1 system.The missing values are filled with mean filling and regression filling respectively in the condition of different coefficients of autocorrelation,effect sizes and missing ratios by SPSS 25.0 software.Bayesian models are built to estimate the posterior means by Winbugs 14 software.Results:When the missing ratio is relatively small,e.g.5%,missing values have relatively little effect on the results.Therapeutic effects may be underestimated when the coefficient of autocorrelation increases and no filling is used.However,it may be overestimated when mean or regression filling is used,and the results after mean filling are closer to the actual effect than regression filling.In the case of moderate missing ratio,the estimated effect after mean filling is closer to the actual effect compared to regression filling.When a large missing ratio(20%)occurs,data missing can lead to significantly underestimate the effect.In this case,the estimated effect after regression filling is closer to the actual effect compared to mean filling.Conclusion:Data missing can affect the estimated therapeutic effects using Bayesian models in N-of-1 trials.The present study suggests that mean filling can be used under situation of missing ratio≤10%.Otherwise,regression filling may be preferable.展开更多
目的通过Meta分析探讨甲状腺癌组织中黏蛋白1(MUC1)表达的临床意义及其与各临床病理参数的相关性。方法检索维普、万方、中国知网、中国生物医学文献、PubMed、Web of Science、Embase、Cochrane中英文数据库中关于MUC1在甲状腺癌中表...目的通过Meta分析探讨甲状腺癌组织中黏蛋白1(MUC1)表达的临床意义及其与各临床病理参数的相关性。方法检索维普、万方、中国知网、中国生物医学文献、PubMed、Web of Science、Embase、Cochrane中英文数据库中关于MUC1在甲状腺癌中表达及其意义的文献,以比值比(OR)和95%置信区间(95%CI)为效应指标,采用STATA 14软件进行Meta分析,并对发表偏倚及敏感性进行检验。结果共纳入13项病例对照研究,甲状腺癌病例组共1157例,非甲状腺癌对照组共509例。结果显示,甲状腺癌病例组MUC1表达明显高于非甲状腺癌对照组(OR=9.78,95%CI:7.49~12.78,P<0.001);伴有淋巴结转移的甲状腺癌组织中MUC1表达高于无淋巴结转移的甲状腺癌组织(OR=3.08,95%CI:1.37~6.92,P<0.05);TNM分期为Ⅲ~Ⅳ期的甲状腺癌组织中MUC1表达高于TNM分期为Ⅰ~Ⅱ期的甲状腺癌组织(OR=1.88,95%CI:1.22~2.90,P<0.05)。结论与非甲状腺癌对照组比较,甲状腺癌病例组MUC1呈高表达,且MUC1高表达与淋巴结转移、TNM分期密切相关。MUC1与甲状腺癌的发生和发展存在相关性,有望成为甲状腺癌分子研究领域的一项新靶标。展开更多
The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centere...The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.展开更多
Background: Protein kinase B (AKT/PKB) family is frequently amplified in ovarian cancer (OC). To the greatest of our knowledge, there is a lack of published reports about the amplification of the genes belonging to th...Background: Protein kinase B (AKT/PKB) family is frequently amplified in ovarian cancer (OC). To the greatest of our knowledge, there is a lack of published reports about the amplification of the genes belonging to the AKT family among Sudanese women with OC. The present study was conducted to detect the AKT1 gene amplification and its association with tumour types, grades, and ages among Sudanese women with OC, bearing in mind the ethnic variation. Methods: This institution-based study included 79 cases of women diagnosed with ovarian cancer (OC) at Omdurman Maternity Hospital in the period 2013-2018. Formalin-fixed, paraffin-embedded (FFPE) tissue sections were used to extract RNA. AKT1 gene amplification was assessed using quantitative real-time PCR. Results: The mean age (±SD) of included women was 49.29 (±13.612). The amplification of AKT1 gene was observed in 18/79 (22.8%) of OC women, with a high frequency in women with undifferentiated 1/2 (50%), clear cell 2/6 (33.3%), mucinous 3/11 (27.3%), endometrioid 3/17 (17.6%), and serous carcinomas 5/30 OC (16.7%). High frequency was seen in women with low (26.3%;n = 10/28) rather than in higher (19.5%;n = 8/33) grade carcinoma, and in older (25.8%;n = 8/23) rather than younger (18.2%;n = 2/9) women. No significant association between AKT1 gene amplification and tumour types, grades, and ages of women was observed (Fisher’s Exact test: p = 0.405, 0.593 and 0.851, respectively). Conclusion: AKT1 gene amplification arises in around one-fifth of Sudanese women with ovarian cancer (OC). It is seen more in undifferentiated, clear cell, and mucinous tumours types, and more frequently in low tumour grade and older women, but not to a statistically significant level. These outcomes sustenance previous studies suggesting that activated AKT genes have a vital role in OC progression and may offer a plan for targeted therapy and prognostic evaluation.展开更多
BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the compa...BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the comparative efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC remain unclear.AIM To compare the efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC.METHODS We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th,2022.We analyzed demographic,medical recorded,histopathologic characteristics,imaging and endoscopic,and follow-up data.The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments.Inverse probability of treatment weighting(IPTW)was used to minimize potential confounding factors.RESULTS We retrospectively analyzed patients who underwent ESD(n=99)or surgery(n=220)or d-CRT(n=16)at the Sun Yat-sen University Cancer Center from 2017 to 2019.The median follow-up time for the ESD group,the surgery group,and the d-CRT group was 42.0 mo(95%CI:35.0-60.2),45.0 mo(95%CI:34.0-61.75)and 32.5 mo(95%CI:28.3-40.0),respectively.After adjusting for background factors using IPTW,the highest 3-year overall survival(OS)rate and 3-year recurrence-free survival(RFS)rate were observed in the ESD group(3-year OS:99.7% and 94.7% and 79.1%;and 3-year RFS:98.3%,87.4% and 79.1%,in the ESD,surgical,and d-CRT groups,respectively).There was no difference of severe complications occurring between the three groups(P≥0.05).Multivariate analysis showed that treatment method,histology and depth of infiltration were independently associated with OS and RFS.CONCLUSION For cT1N0M0 EC,ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery,with a similar rate of severe complications occurring.展开更多
基金supported by the National Natural Science Foundation of China (No.81973705).
文摘Background:Missing data are frequently occurred in clinical studies.Due to the development of precision medicine,there is an increased interest in N-of-1 trial.Bayesian models are one of main statistical methods for analyzing the data of N-of-1 trials.This simulation study aimed to compare two statistical methods for handling missing values of quantitative data in Bayesian N-of-1 trials.Methods:The simulated data of N-of-1 trials with different coefficients of autocorrelation,effect sizes and missing ratios are obtained by SAS 9.1 system.The missing values are filled with mean filling and regression filling respectively in the condition of different coefficients of autocorrelation,effect sizes and missing ratios by SPSS 25.0 software.Bayesian models are built to estimate the posterior means by Winbugs 14 software.Results:When the missing ratio is relatively small,e.g.5%,missing values have relatively little effect on the results.Therapeutic effects may be underestimated when the coefficient of autocorrelation increases and no filling is used.However,it may be overestimated when mean or regression filling is used,and the results after mean filling are closer to the actual effect than regression filling.In the case of moderate missing ratio,the estimated effect after mean filling is closer to the actual effect compared to regression filling.When a large missing ratio(20%)occurs,data missing can lead to significantly underestimate the effect.In this case,the estimated effect after regression filling is closer to the actual effect compared to mean filling.Conclusion:Data missing can affect the estimated therapeutic effects using Bayesian models in N-of-1 trials.The present study suggests that mean filling can be used under situation of missing ratio≤10%.Otherwise,regression filling may be preferable.
文摘目的通过Meta分析探讨甲状腺癌组织中黏蛋白1(MUC1)表达的临床意义及其与各临床病理参数的相关性。方法检索维普、万方、中国知网、中国生物医学文献、PubMed、Web of Science、Embase、Cochrane中英文数据库中关于MUC1在甲状腺癌中表达及其意义的文献,以比值比(OR)和95%置信区间(95%CI)为效应指标,采用STATA 14软件进行Meta分析,并对发表偏倚及敏感性进行检验。结果共纳入13项病例对照研究,甲状腺癌病例组共1157例,非甲状腺癌对照组共509例。结果显示,甲状腺癌病例组MUC1表达明显高于非甲状腺癌对照组(OR=9.78,95%CI:7.49~12.78,P<0.001);伴有淋巴结转移的甲状腺癌组织中MUC1表达高于无淋巴结转移的甲状腺癌组织(OR=3.08,95%CI:1.37~6.92,P<0.05);TNM分期为Ⅲ~Ⅳ期的甲状腺癌组织中MUC1表达高于TNM分期为Ⅰ~Ⅱ期的甲状腺癌组织(OR=1.88,95%CI:1.22~2.90,P<0.05)。结论与非甲状腺癌对照组比较,甲状腺癌病例组MUC1呈高表达,且MUC1高表达与淋巴结转移、TNM分期密切相关。MUC1与甲状腺癌的发生和发展存在相关性,有望成为甲状腺癌分子研究领域的一项新靶标。
文摘The intricacies of Alzheimer’s disease pathogenesis are being increasingly illuminated by the exploration of epigenetic mechanisms,particularly DNA methylation.This review comprehensively surveys recent human-centered studies that investigate whole genome DNA methylation in Alzheimer’s disease neuropathology.The examination of various brain regions reveals distinctive DNA methylation patterns that associate with the Braak stage and Alzheimer’s disease progression.The entorhinal cortex emerges as a focal point due to its early histological alterations and subsequent impact on downstream regions like the hippocampus.Notably,ANK1 hypermethylation,a protein implicated in neurofibrillary tangle formation,was recurrently identified in the entorhinal cortex.Further,the middle temporal gyrus and prefrontal cortex were shown to exhibit significant hypermethylation of genes like HOXA3,RHBDF2,and MCF2L,potentially influencing neuroinflammatory processes.The complex role of BIN1 in late-onset Alzheimer’s disease is underscored by its association with altered methylation patterns.Despite the disparities across studies,these findings highlight the intricate interplay between epigenetic modifications and Alzheimer’s disease pathology.Future research efforts should address methodological variations,incorporate diverse cohorts,and consider environmental factors to unravel the nuanced epigenetic landscape underlying Alzheimer’s disease progression.
文摘Background: Protein kinase B (AKT/PKB) family is frequently amplified in ovarian cancer (OC). To the greatest of our knowledge, there is a lack of published reports about the amplification of the genes belonging to the AKT family among Sudanese women with OC. The present study was conducted to detect the AKT1 gene amplification and its association with tumour types, grades, and ages among Sudanese women with OC, bearing in mind the ethnic variation. Methods: This institution-based study included 79 cases of women diagnosed with ovarian cancer (OC) at Omdurman Maternity Hospital in the period 2013-2018. Formalin-fixed, paraffin-embedded (FFPE) tissue sections were used to extract RNA. AKT1 gene amplification was assessed using quantitative real-time PCR. Results: The mean age (±SD) of included women was 49.29 (±13.612). The amplification of AKT1 gene was observed in 18/79 (22.8%) of OC women, with a high frequency in women with undifferentiated 1/2 (50%), clear cell 2/6 (33.3%), mucinous 3/11 (27.3%), endometrioid 3/17 (17.6%), and serous carcinomas 5/30 OC (16.7%). High frequency was seen in women with low (26.3%;n = 10/28) rather than in higher (19.5%;n = 8/33) grade carcinoma, and in older (25.8%;n = 8/23) rather than younger (18.2%;n = 2/9) women. No significant association between AKT1 gene amplification and tumour types, grades, and ages of women was observed (Fisher’s Exact test: p = 0.405, 0.593 and 0.851, respectively). Conclusion: AKT1 gene amplification arises in around one-fifth of Sudanese women with ovarian cancer (OC). It is seen more in undifferentiated, clear cell, and mucinous tumours types, and more frequently in low tumour grade and older women, but not to a statistically significant level. These outcomes sustenance previous studies suggesting that activated AKT genes have a vital role in OC progression and may offer a plan for targeted therapy and prognostic evaluation.
基金Supported by the Guangdong Esophageal Cancer Institute Science and Technology Program,No.M202013Guangdong Medical Research Foundation,No.A2021369.
文摘BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the comparative efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC remain unclear.AIM To compare the efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC.METHODS We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th,2022.We analyzed demographic,medical recorded,histopathologic characteristics,imaging and endoscopic,and follow-up data.The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments.Inverse probability of treatment weighting(IPTW)was used to minimize potential confounding factors.RESULTS We retrospectively analyzed patients who underwent ESD(n=99)or surgery(n=220)or d-CRT(n=16)at the Sun Yat-sen University Cancer Center from 2017 to 2019.The median follow-up time for the ESD group,the surgery group,and the d-CRT group was 42.0 mo(95%CI:35.0-60.2),45.0 mo(95%CI:34.0-61.75)and 32.5 mo(95%CI:28.3-40.0),respectively.After adjusting for background factors using IPTW,the highest 3-year overall survival(OS)rate and 3-year recurrence-free survival(RFS)rate were observed in the ESD group(3-year OS:99.7% and 94.7% and 79.1%;and 3-year RFS:98.3%,87.4% and 79.1%,in the ESD,surgical,and d-CRT groups,respectively).There was no difference of severe complications occurring between the three groups(P≥0.05).Multivariate analysis showed that treatment method,histology and depth of infiltration were independently associated with OS and RFS.CONCLUSION For cT1N0M0 EC,ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery,with a similar rate of severe complications occurring.
