1.Causal association between plasma phosphatidylethanolamine and risk of colorectal adenocarcinoma:a two-sample Mendelian randomization study
Ling XU ; Yuchan HUANGFU ; Lisong SHEN ; Yanhui MA
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(5):605-613
Objective·To employ the two-sample Mendelian randomization(TSMR)method,using genetic variants as instrumental variables,to investigate the causal relationship between phosphatidylethanolamine(PE)and the risk of colorectal adenocarcinoma.Methods·The single-nucleotide polymorphism(SNP)data associated with PE and colorectal adenocarcinoma were obtained from the Medical Research Council Integrative Epidemiology Unit(MRC IEU)at the University of Bristol and the Finnish Biobank,respectively.A secondary data analysis was conducted using summary statistics from genome-wide association studies(GWAS),and genetic loci strongly associated with PE were selected as instrumental variables.Four Mendelian randomization(MR)methods,inverse-variance weighted(IVW)method,MR-Egger regression,weighted median(WME)method,and weighted mode(WM)method,were employed to assess the causal effect.The IVW method was used as the primary statistical approach,while MR-Egger,WME,and WM served as supplementary methods.Rigorous assessments for robustness included MR-Egger regression,MR-PRESSO global tests for horizontal pleiotropy,and Cochran's Q test to evaluate heterogeneity.Results·Ten instrumental variables were selected,and the Steiger test indicated that all PE-associated SNPs exhibited a consistent direction of causal effect on colorectal cancer.Among the 10 SNPs,rs102275 and rs9393903 showed the strongest positive associations with colorectal adenocarcinoma risk,with effect sizes of 0.45(P=8.01×10-5)and 0.82(P=2.31×10-2),respectively.Consistent findings from MR analyses demonstrated that PE elevated the risk of colorectal adenocarcinoma across all four methods.In the IVW analysis,the OR was 1.36(95%CI 1.17?1.59,P=7.24×10-5).In the MR-Egger regression,the OR was 1.44(95%CI 0.97?2.14,P=1.12×10-1).In the WEM analysis,the OR was 1.33(95%CI 1.07?1.65,P=8.81×10-3).In the WM analysis,the OR was 1.41(95%CI 1.12?1.77,P=1.70×10-2).Cochran's Q test revealed no heterogeneity among the effect estimates of the 10 SNPs on colorectal adenocarcinoma.Both MR-Egger regression intercept and MR-PRESSO test indicated no evidence of horizontal pleiotropy among the SNPs.Leave-one-out analysis showed overlapping confidence intervals after excluding any single SNP,indicating that the results were not sensitive to individual SNPs and were highly robust.Conclusions·There is a causal association between circulating PE levels and the risk of colorectal adenocarcinoma.A genetically predicted increase of one standard deviation in plasma PE levels is associated with a 1.36-fold higher risk of developing colorectal adenocarcinoma(95%CI 1.17?1.59,P=7.24×10-5).
2.Causal association between plasma phosphatidylethanolamine and risk of colorectal adenocarcinoma:a two-sample Mendelian randomization study
Ling XU ; Yuchan HUANGFU ; Lisong SHEN ; Yanhui MA
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(5):605-613
Objective·To employ the two-sample Mendelian randomization(TSMR)method,using genetic variants as instrumental variables,to investigate the causal relationship between phosphatidylethanolamine(PE)and the risk of colorectal adenocarcinoma.Methods·The single-nucleotide polymorphism(SNP)data associated with PE and colorectal adenocarcinoma were obtained from the Medical Research Council Integrative Epidemiology Unit(MRC IEU)at the University of Bristol and the Finnish Biobank,respectively.A secondary data analysis was conducted using summary statistics from genome-wide association studies(GWAS),and genetic loci strongly associated with PE were selected as instrumental variables.Four Mendelian randomization(MR)methods,inverse-variance weighted(IVW)method,MR-Egger regression,weighted median(WME)method,and weighted mode(WM)method,were employed to assess the causal effect.The IVW method was used as the primary statistical approach,while MR-Egger,WME,and WM served as supplementary methods.Rigorous assessments for robustness included MR-Egger regression,MR-PRESSO global tests for horizontal pleiotropy,and Cochran's Q test to evaluate heterogeneity.Results·Ten instrumental variables were selected,and the Steiger test indicated that all PE-associated SNPs exhibited a consistent direction of causal effect on colorectal cancer.Among the 10 SNPs,rs102275 and rs9393903 showed the strongest positive associations with colorectal adenocarcinoma risk,with effect sizes of 0.45(P=8.01×10-5)and 0.82(P=2.31×10-2),respectively.Consistent findings from MR analyses demonstrated that PE elevated the risk of colorectal adenocarcinoma across all four methods.In the IVW analysis,the OR was 1.36(95%CI 1.17?1.59,P=7.24×10-5).In the MR-Egger regression,the OR was 1.44(95%CI 0.97?2.14,P=1.12×10-1).In the WEM analysis,the OR was 1.33(95%CI 1.07?1.65,P=8.81×10-3).In the WM analysis,the OR was 1.41(95%CI 1.12?1.77,P=1.70×10-2).Cochran's Q test revealed no heterogeneity among the effect estimates of the 10 SNPs on colorectal adenocarcinoma.Both MR-Egger regression intercept and MR-PRESSO test indicated no evidence of horizontal pleiotropy among the SNPs.Leave-one-out analysis showed overlapping confidence intervals after excluding any single SNP,indicating that the results were not sensitive to individual SNPs and were highly robust.Conclusions·There is a causal association between circulating PE levels and the risk of colorectal adenocarcinoma.A genetically predicted increase of one standard deviation in plasma PE levels is associated with a 1.36-fold higher risk of developing colorectal adenocarcinoma(95%CI 1.17?1.59,P=7.24×10-5).
3.Mechanisms and perspectives of B vitamins associated one carbon metabolism on colorectal cancer risk
Yanhui MA ; Lisong SHEN ; Yingxia ZHENG
Chinese Journal of Preventive Medicine 2024;58(11):1739-1751
Colorectal cancer (CRC) represents a significant global health challenge as a common malignancy of the digestive tract. The involvement of B vitamins—specifically folic acid (B9), riboflavin (B2), pyridoxine (B6), and cobalamin (B12)—is crucial in metabolic processes by mediating the transfer of one-carbon (1C) units, which plays a fundamental role in cellular functions and tumor growth. 1C metabolism is involved in synthesis of proteins, lipids, nucleic acids, and other cofactors. 1C metabolism, intertwined with the metabolism of other nutrients, forms complex pathways where B vitamins act as precursors or coenzymes, influencing the production of various intermediates. These vitamins, as essential nutrients, are implicated to varying the pathogenesis and progression of colorectal cancer such as epigenetics. Furthermore, 1C metabolism affects tumor cell fate through multiple aspects including nucleotide synthesis, redox homeostasis, and the interaction with gut microbiota. Given these roles, understanding and monitoring B vitamin levels and their metabolic pathways are essential for colorectal cancer prevention and management. This approach not only helps in reducing tumor-related mortality but also opens new avenues for research into CRC mechanisms and potential therapeutic strategies.
4.Mechanisms and perspectives of B vitamins associated one carbon metabolism on colorectal cancer risk
Yanhui MA ; Lisong SHEN ; Yingxia ZHENG
Chinese Journal of Preventive Medicine 2024;58(11):1739-1751
Colorectal cancer (CRC) represents a significant global health challenge as a common malignancy of the digestive tract. The involvement of B vitamins—specifically folic acid (B9), riboflavin (B2), pyridoxine (B6), and cobalamin (B12)—is crucial in metabolic processes by mediating the transfer of one-carbon (1C) units, which plays a fundamental role in cellular functions and tumor growth. 1C metabolism is involved in synthesis of proteins, lipids, nucleic acids, and other cofactors. 1C metabolism, intertwined with the metabolism of other nutrients, forms complex pathways where B vitamins act as precursors or coenzymes, influencing the production of various intermediates. These vitamins, as essential nutrients, are implicated to varying the pathogenesis and progression of colorectal cancer such as epigenetics. Furthermore, 1C metabolism affects tumor cell fate through multiple aspects including nucleotide synthesis, redox homeostasis, and the interaction with gut microbiota. Given these roles, understanding and monitoring B vitamin levels and their metabolic pathways are essential for colorectal cancer prevention and management. This approach not only helps in reducing tumor-related mortality but also opens new avenues for research into CRC mechanisms and potential therapeutic strategies.
5.Potential of new self-crosslinked hyaluronic acid gel on the recovery of endometrium after artificial abortion: a multicenter, prospective randomized controlled trial
Chunying LI ; Lirong TENG ; Qing LIN ; Liping ZHAO ; Yunxia ZHU ; Xin MI ; Zhenna WANG ; Xiaoye WANG ; Lisong ZHANG ; Dan HAN ; Lili MA ; Wenpei BAI ; Jianmei WANG ; Jun NI ; Huiping SHEN ; Qinfang CHEN ; Hongmei XU ; Chenchen REN ; Jing JIANG ; Guanyuan LIU ; Ping PENG ; Xinyan LIU
Chinese Journal of Obstetrics and Gynecology 2024;59(11):864-870
Objective:To evaluate the impact of self-crosslinked hyaluronic acid (SCH) gel on endometrium recovery after artificial abortion.Methods:A multicenter, prospective randomized controlled trial was conducted across 18 hospitals from December 2021 to February 2023, involving 382 women who underwent artificial abortion. Participants were randomly allocated to receive either treatment with SCH gel (SCH group) or no treatment (control group) in a 1∶1 ratio. The primary outcome was endometrium thickness in 14 to 18 days after the first postoperative menstruation. Secondary outcomes included changes in menstrual volume during the first postoperative menstruation, menstruation resumption within 6 postoperative weeks, time to menstruation resumption, duration of the first postoperative menstruation, and incidence of dysmenorrhea.Results:Baseline characteristics of participants were comparable between the two groups (all P>0.05), with 95.3% (182/191) in SCH group and 92.7% (177/191) in the control group completed the study. The postoperative endometrial thickness in SCH group was significantly greater than that in the control group [(9.78±3.15) vs (8.95±2.32) mm; P=0.005]. SCH group also had significantly fewer participants with reduced menstrual volume [23 cases (12.6%, 23/182) vs 31 cases (17.5%, 31/177); P=0.038]. Although SCH group experienced less dysmenorrhea during the first postoperative menstrual period, this difference was not statistically significant [28.5% (51/179) vs 37.1% (65/175); P=0.083]. Outcomes were similar between SCH group and the control group regarding the proportion of participants who resumed menstruation within 6 weeks postoperatively, time to menstruation resumption, and duration of the first postoperative menstruation ( P=0.792, 0.485, and 0.254, respectively). No serious adverse events were observed during the study period, and no adverse events were attributed to SCH gel treatment. Conclusion:The application of SCH gel after artificial abortion is safe and might aid in the recovery of the endometrium.
6.Application of deep learning in immunofluorescence images recognition of antinuclear antibodies
Junxiang ZENG ; Wenqi JIANG ; Jingxu XU ; Yahui AN ; Chencui HUANG ; Xiupan GAO ; Youyou YU ; Xiujun PAN ; Lisong SHEN
Chinese Journal of Laboratory Medicine 2023;46(10):1094-1098
Objective:To develop a prototype artificial intelligence immunofluorescence image recognition system for classification of antinuclear antibodies in order to meet the growing clinical requirements for an automatic readout and classification of immunof luorescence patterns for antinuclear antibody (ANA) images.Methods:Immunofluorescence images with positive results of ANA in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 2020 to December 2021 were collected. Three senior technicians independently and in parallel interpreted the Immunofluorescence images to determine the ANA results. Then the images were labeled according to the ANA International Consensus on Fluorescence Patterns (ICAP) classification criteria. There were 7 labeled groups: Fine speckled, Coarse speckled, Homogeneous, nucleolar, Centromere, Nuclear dots and Nuclear envelope. Each group was randomly divided into training dataset and validation dataset at a ratio of 9∶1 by using random number table. On the deep learning framework PyTORCH 1.7, the convolutional neural network (CNN) training platform was constructed based on ResNet-34 image classification network, and the automatic ANA recognition system was established. After the model was established, the test set was set up separately, the judgment results of the model were output by ranking the prediction probability, with the results of the 2 senior technicians was taken as "golden standard". Parameters such as accuracy, precision, recall and F1-score were used as indicators to evaluate the performance of the model.Results:A total of 23138 immunofluorescence images were obtained after segmentation and annotation. A total of 7 models were trained, and the effects of different algorithms, image processing and enhancement methods on the model were compared. The ResNet-34 model with the highest accuracy andswas selected as the final model, with the classification accuracy of 93.31%, precision rate of 91%, and recall rate of 90% and F1-score of 91% in the test set. The overall coincidence rate between the model and manual interpretation was 90.05%, and the accuracy of recognition of nucleolus was the highest, with the coincidence rate reaching 100% in the test set.Conclusion:The current AI system developed based on deep learning of the ANA immunofluorescence images in the present study showed the ability to recognize ANA pattern, especially in the common, typical, simple pattern.
7.Thinking of the current status and application of machine learning in the field of laboratory medicine
Chinese Journal of Laboratory Medicine 2022;45(12):1197-1200
In recent years, machine learning has become a hot spot in various research fields. Using machine learning can realize the transformation from data driven to knowledge discovery, which is an important development direction of laboratory intelligence in the future. The application of machine learning in laboratory medicine has shown great potential, but t it also has many challenges and difficulties. The direction of our joint efforts is to promote the clinical transformation of machine learning technology, realize the practicality and industrialization in medical laboratories, and achieve the goal of assisting clinical decision-making as soon as possible.
8.Application of deep learning in antinuclear antibodies classification: progress and challenges
Chinese Journal of Laboratory Medicine 2021;44(10):877-881
Antinuclear antibodies (ANA) testing is essential for the diagnosis, classification, and disease activity monitoring of systemic autoimmune rheumatic diseases. In recent years, with the enhancement of computing power and the innovation of algorithms, the newly hip branch, deep learning (DL), practically delivered all of the most stunning achievements and breakthroughs in artificial intelligence (AI) so far. The application of DL to visual tasks, known as computer vision, has revealed significant power within the medical image recognition. Indirect immunofluorescence on HEp-2 cells is the reference method for ANA testing, the results is interpreted manually by specialized physicians. ANA fluorescent pattern classification is based on image recognition, which has a broad prospect of combining with DL to realize automatic interpretation system. This paper reviews the recent research progress and challenges of DL in the field of ANA detection in order to provide references for the standardization of ANA testing in the future.
9.Progress in the traceability of tumor marker detection
Chinese Journal of Preventive Medicine 2021;55(4):545-550
Tumor markers (TM) detection is of great significance in tumor screening, monitoring and treatment intervention, which puts forward higher requirements for its detection quality. TM traceability is very important in the process of reagent production and clinical laboratory testing, which can help improving the reliability and comparability of TM testing. Based on the current principles and classification system of metrology traceability in the world, this paper reviews the quality requirements of reference materials and reference measurement methods related to protein and nucleic acid of TM, as well as the problems existing in the international convention reference measurement procedure and traceability system of TM, so as to provide a new idea for the quality assurance work of TM detection.
10.Progress in the traceability of tumor marker detection
Chinese Journal of Preventive Medicine 2021;55(4):545-550
Tumor markers (TM) detection is of great significance in tumor screening, monitoring and treatment intervention, which puts forward higher requirements for its detection quality. TM traceability is very important in the process of reagent production and clinical laboratory testing, which can help improving the reliability and comparability of TM testing. Based on the current principles and classification system of metrology traceability in the world, this paper reviews the quality requirements of reference materials and reference measurement methods related to protein and nucleic acid of TM, as well as the problems existing in the international convention reference measurement procedure and traceability system of TM, so as to provide a new idea for the quality assurance work of TM detection.

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