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  • Reviews
    Chen ZHU, Rui LIU, Yun-yun REN
    Fudan University Journal of Medical Sciences. 2024, 51(02): 268-271. https://doi.org/10.3969/j.issn.1672-8467.2024.02.019

    Ultrasound measurement of fetal biological parameters is an important indicator for evaluating fetal intrauterine growth and development, and its corresponding fetal growth standards are important criteria for determining whether the measurement parameters are normal or have fetal growth restriction. There are classic regional standards of prenatal ultrasonic measurement that have been used for many years, as well as international standards that have received widespread attention in recent years. However, there is no unified global standard. This paper reviewed the development process and clinical application status of fetal growth standards, explore future research trends, with a view to providing reference value for clinical practice.

  • Papers
    Ke LIN, Li-jun WU, Ji-bin XIN, Jun YING, Wen-hong ZHANG
    Fudan University Journal of Medical Sciences. 2024, 51(02): 181-190. https://doi.org/10.3969/j.issn.1672-8467.2024.02.006

    Objective: By analyzing relevant literature of long COVID, we aimed to understand the current research status, hotspots and trends in this field. Methods: Based on Web of Science core collection data, bibliometric analysis was used as the main research method. The results were visualized with VOSviewer. A comprehensive analysis was performed from various perspectives including trends in publication, journal distribution, highly cited papers, international research collaboration networks, and clusters of keywords, etc. Results: The field of long COVID has garnered significant global academic attention. A total of 7 877 related articles were retrievable, with a total citation count of 103 389 and an average citation count of 13.13 per article. Among them, the United States published the most articles (1 780 articles, 22.59%), while China ranked fifth in publication volume (686 articles, 8.71%). The international scientific cooperation network reflected the close collaborative relationships between countries in long COVID research, predominantly involving the United States, the United Kingdom, Italy, India, and China. Keywords clustering indicated that the current main research focuses in the long COVID field include: clinical manifestations, epidemiological characteristics, risk factors, and mechanisms of occurrence, treatment and rehabilitation measures of long COVID, and its impact on public and social life. Conclusion: This article reveals the current state, research hotspots and trends in the long COVID field, providing valuable references for related research institutions, scholars as well as health administrative office.

  • Lecture
    Ya-hang LIU, Yong-fu YU, Guo-you QIN
    Fudan University Journal of Medical Sciences. 2024, 51(02): 280-284. https://doi.org/10.3969/j.issn.1672-8467.2024.02.022

    This article introduced the basic theory of non-parametric regression and its application in medical and public health research for methodological reference. We conducted Cox proportional hazard models with restricted cubic splines using chronic disease management data from a Center for Disease Control and Prevention. We aimed to explore the separate and combined effects of mean fasting blood glucose level and glucose variability on all-cause mortality among individuals with type 2 diabetes. A non-linear association was observed between glucose variability and the risk of all-cause mortality. The association between glucose variability and all-cause mortality was stronger at higher mean fasting blood glucose levels compared to lower levels. The non-parametric regression methods comprehensively explored dose-response relationships between continuous exposure and outcome, revealing the combined effects of continuous exposures, which provided recommendations for targeted interventions. The method showed promising application value in medical and public health research.

  • Papers
    Xu-chun SONG, Ji-chun ZHOU, Xu-dong LYU
    Fudan University Journal of Medical Sciences. 2024, 51(04): 443-454. https://doi.org/10.3969/j.issn.1672-8467.2024.04.001

    Objective: To compare the performance of machine learning (ML) and individualized treatment effect (ITE) models based on deep learning in providing personalized treatment recommendations using real-world clinical datasets, and construct personalized drug treatment recommendation models for pegylated liposomal doxorubicin (PLD) and epirubicin (EPI) in postoperative breast cancer patients, and assist clinical decision-making by evaluating the treatment effects of these drugs. Methods: Clinical data of 904 breast cancer patients admitted at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine was collected retrospectively, including 387 cases treated with PLD and 517 cases treated with EPI. The two groups were compared using propensity score matching to assess the 5-year disease free survival (DFS) outcome. Six ITE models, including CFR_WASS, were used to predict the 5-year DFS probability of patients under two drug treatments. Six machine learning (ML) models, including Random Forest, were used as baselines for performance analysis and comparison. Model's Predictive performance was evaluated based on the AUROC. The effectiveness of treatment recommendations was assessed by calculating the difference of 5-year rates between the group where the actual treatment used was consistent with the treatment recommended by the model and the control group. Results: Among the 153 matched cases, there was no statistically significant difference in 5-year DFS outcomes between the two groups. In 16 pairs of cases, the PLD group showed better clinical outcomes than the EPI group, and in 12 pairs of cases, the EPI group had better clinical outcomes than the PLD group, confirming individual differences in treatment benefit between the two drugs. The CFR_WASS model achieved the optimal predictive performance (AUROC value was 0.736 8), and there was no significant difference in 5-year DFS rates between most ML groups and the control group; The 5-year DFS rate in the ITE group was lower than that in the control group (P < 0.01), showing significant differences. Among them, the 5-year DFS rate in the CFR_WASS group was 2.13% lower than that in the control group. Conclusion: The ITE model is more accurate in estimating the individualized treatment effects of two drugs compared to the ordinary ML model, providing effective individualized treatment recommendations, and has certain clinical application value.

  • Lecture
    Chen HUANG, Yong-fu YU, Guo-you QIN
    Fudan University Journal of Medical Sciences. 2024, 51(04): 638-642. https://doi.org/10.3969/j.issn.1672-8467.2024.04.025

    Propensity score weighting methods are crucial tools for adjusting confounding and conducting causal inference in observational studies. This paper introduces various propensity score weighting methods, and details the key features of each to aid researchers in selecting the most suitable method for their analyses. Additionally, the application of these methods in the fields of medicine and public health is demonstrated through an example data analysis. The example is based on data from 996 patients who underwent percutaneous coronary intervention (PCI). Different propensity score weighting methods are used to explore the effect of PCI combined with abciximab on six-month post-operative survival rates. The results indicate that different propensity score weighting methods provide treatment effect estimates tailored to different inference goals, highlighting the importance of selecting the appropriate method based on the specific inference objective. Propensity score weighting methods enhance the balance of covariate distribution between treatment and control groups, making them powerful tools for adjusting confounding factors in observational studies. Their applicability and value in medical and public health research are significant.

  • Reviews
    Ya-kun ZHANG, Bei-li WANG, Wei GUO
    Fudan University Journal of Medical Sciences. 2024, 51(02): 262-267. https://doi.org/10.3969/j.issn.1672-8467.2024.02.018

    Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease that ranges from relatively benign hepatic steatosis to nonalcoholic steatohepatitis (NASH). NASH is characterized by persistent liver damage, inflammation, and fibrosis which significantly increases the risk of end-stage liver diseases, such as liver cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD/NASH is not yet fully understood, but its recent epigenetic advances have provided new insights into the mechanisms of this disease. This review summarized recent progress in this area which has laid a solid foundation for elucidating the pathogenesis of NAFLD and provides potential targets for early detection, diagnosis, and treatment of this disease.

  • Papers
    Heng-yi ZHOU, Jing LI, Dan-hua DAI, Yang LI, Bin ZHANG, Rong DU, Rui-long WU, Jia-yan JIANG, Yuan-man WEI, Jing-rong GAO, Qi ZHAO
    Fudan University Journal of Medical Sciences. 2024, 51(02): 143-150. https://doi.org/10.3969/j.issn.1672-8467.2024.02.001
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    Objective: To explore the relationship and internal path between activities of daily living (ADL), sleep quality and mental health of community elderly people in Shanghai. Methods: A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec, 2021 using convenience sampling. Activities of Daily Living (ADL), Pittsburgh Sleep Quality Index (PSQI) and 10-item Kessler Psychological Distress Scale (K10) were adopted in the survey. Single factor analysis, correlation analysis and multiple linear regression were used to analyze the data. The effect relationship between the variables was tested using Bootstrap's mediated effects test. Results: A total of 1 864 participants were included in the study. The average score was 15.53±4.47 for ADL, 5.60±3.71 for PSQI and 15.50±6.28 for K10. The rate of ADL impairment, poor sleep quality, poor and very poor mental health of the elderly were 23.6%, 27.3%, 11.9% and 4.9%, respectively. ADL and sleep quality were all positively correlated with mental health(r=0.321, P < 0.001; r=0.466, P < 0.001); ADL was positively correlated with sleep quality(r=0.294, P < 0.001). Multiple linear results of factors influencing mental health showed that ADL (β=0.457, 95%CI: 0.341-0.573), sleep quality(β=0.667, 95%CI: 0.598-0.737) and mental health were positively correlated (P < 0.001). Sleep quality partially mediated the relationship between ADL and mental health (95%CI: 0.078-0.124) with an effect size of 33.0%. Conclusion: Sleep quality is a mediator between ADL and mental health among community elderly people. Improving ADL and sleep quality may improve mental health in the population.

  • Reviews
    Yan WANG, Ru-he JIANG, Yue YU, Yan DU
    Fudan University Journal of Medical Sciences. 2024, 51(04): 620-631. https://doi.org/10.3969/j.issn.1672-8467.2024.04.023

    Cantharidin is a terpenoid compound secreted by Mylabrisphalerata Pallas. In a variety of cancer types, cantharidin has shown the effects of inhibiting cancer cell growth, proliferation and migration. The anticancer mechanism of cantharidin involves inducing cell cycle arrest and apoptosis, inhibiting autophagy, enhancing DNA damage, inhibiting DNA repair, and regulating various cell signaling pathways. This article reviews the mechanism and research progress of cantharidin and its derivatives in common cancer types, in order to identify novel targets of cancer treatment using cantharidin, and provide new direction for clinical research to improve anticancer therapy.

  • Papers
    Yu-hua LIU, Hai-yan LU, Jing ZENG, Wei-ying WANG
    Fudan University Journal of Medical Sciences. 2024, 51(02): 205-210. https://doi.org/10.3969/j.issn.1672-8467.2024.02.009

    Objective: To explore the operation effect of the improved full-appointment mode of ambulatory chemotherapy, so as to provide reference for further improving the treatment process. Methods: The enhanced full-appointment mode had been implemented in Fudan University Shanghai Cancer Center outpatient information system, which seamlessly integrated daytime chemotherapy assessment with comprehensive information management, formulated precise rules for chemotherapy appointments, and ensured efficient integration of relevant data.A comparative analysis was conducted between the period after optimization (Jan to Sep 2022) and the corresponding period in the previous year (Jan to Sep 2021), considering factors such as patient waiting time, human involvement, patient safety during chemotherapy, as well as nurse and patient satisfaction. Results: After optimization, the time spent by patients was reduced from 52.12 (32.73-83.05) to 20.04 (11.87-41.10) minutes, with statistically significant difference (z=-78.144, P < 0.001). Additionally, the time spent by patients before and after optimization was significantly different in the distribution of < 30 minutes, 30-60 minutes, and > 60 minutes (χ2=5 958.455, P < 0.001). Previously, one nurse and 2-3 security personnel were required to schedule appointments in the daytime chemotherapy center, while after optimization, there was no longer a need for nurses to arrange appointment windows and the number of security personnel was reduced to one, thereby optimized human operations. It was observed that the number of cases involving chemotherapy infusion reactions decreased from 59 to 46 following optimization, and the number of patients requiring rescue observation reduced from four to one. Notably, no rescue events occurred during non-day shifts, thus enhanced patient safety during treatment hours outside regular working hours. Furthermore, there was a statistically significant improvement in both nurses' and patients' satisfaction levels before and after implementation of these optimizations (P < 0.05). Conclusion: The modified full appointment mode reduced patient waiting time, optimized human resources utilization, enhanced patient safety during chemotherapy, and improved satisfaction levels among both nurses and patients. The implementation of the modified full appointment mode for daytime chemotherapy centers was beneficial to their overall operation.

  • Papers
    Le-ying LI, Yao CHEN, Wei-tao ZHOU, Chen HE, Duan-wu ZHANG, Li-ling QIAN
    Fudan University Journal of Medical Sciences. 2024, 51(03): 359-367. https://doi.org/10.3969/j.issn.1672-8467.2024.03.010

    Objective: To study and verify the function of de novo interferon regulatory factor (IRF8) frameshift mutation detected in an etiology screening of the cohort of children with recurrent pneumonia at the molecular level. Methods: The recombinant overexpression plasmids with wildtype or mutated IRF8 genes were constructed to transiently transfect HEK293T cells, or packed into lentivirus to infect two kinds of immune cell lines. Q-PCR, Western blot, immunofluorescence and other experimental assays were performed to explore the differences of expression and the regulatory effect on downstream genes associated with inflammation. Results: The recombinant vectors with wildtype or mutated IRF8 genes were constructed successfully, and the efficiency of transfection by plasmids and infection by packed lentivirus was remarkable as well. Compared with wildtype, the molecular weight of IRF8 variant was slightly increased, while the expression level presents in opposition, even if on transcription level. Moreover, the localization of IRF8 variant was detected in abundance in nucleus rather than cytoplasm, and its inhibition effect was enhanced on the downstream ISRE element in comparison with the wildtype IRF8 protein. Conclusion: The de novo frameshift mutation was presumed as gain-of-function (GOF) mutation.

  • Lecture
    Ke-cheng WEI, Yong-fu YU, Guo-you QIN
    Fudan University Journal of Medical Sciences. 2024, 51(03): 439-442. https://doi.org/10.3969/j.issn.1672-8467.2024.03.022

    This paper briefly introduced the varying coefficient model and used the varying coefficient Cox model as an example to demonstrate its application in the fields of medicine and public health through real data analysis, thereby provided methodological references for related research. The example was based on chronic disease management data from a Center for Disease Control and Prevention, fitting a varying coefficient Cox model to explore the time-varying association between body mass index (BMI) and mortality risk among a hypertensive population. The results showed that being underweight (BMI < 18.5 kg/m2) was associated with a higher risk of mortality, but this association weakened over time; being overweight (23 kg/m2≤BMI < 25 kg/m2) was associated with a lower risk of mortality, and this association also weakened over time. The varying coefficient model captured how the impact of exposure factors on outcomes changed with other variables, helping to comprehensively understand the complex relationships between variables, and had significant application and promotion value in medical and public health research.

  • Reviews
    Xia WANG, Jing YOU, Yue-jiao ZHAO, Hui WANG, Hui-yuan CAI
    Fudan University Journal of Medical Sciences. 2024, 51(05): 837-844. https://doi.org/10.3969/j.issn.1672-8467.2024.05.029

    With the development of genetics and advances in genetic testing technology, the demand for cancer genetic counseling has increased dramatically. Advanced practice nurses play a key role in personalized health care delivery. The oncology genetic nurse-led genetic counseling services in foreign countries are becoming more and more mature, but in China, the work of oncology genetic counseling started late, and the combination of genetics/genomics with nursing is still in its infancy. There is still a lack of relevant research on oncology genetic nurses. This article introduced the qualification certification, core competence and clinical practice content of foreign oncology genetic nurses, and summarized the clinical practice effect of oncology genetic nurses and the enlightenment to China's advanced nursing practice, which provided references for the construction of oncology genetic nurses training programs and clinical service models suitable for China's national conditions, so as to meet the needs of the development of advanced nursing practice and the growing demand for precision oncology and high-quality genetic medical care.

  • Case Reports
    Hui-jie LI, Di ZHANG, Yi-fei ZHONG, Yue-yi DENG, Wen-shu GE
    Fudan University Journal of Medical Sciences. 2024, 51(03): 420-425, 434. https://doi.org/10.3969/j.issn.1672-8467.2024.03.018

    Glomerulocystic kidney disease (GCKD), a rare nephrocystic disorder, was the focus of this study. The FAT1 gene, comprising 27 exons, encoded a single-pass transmembrane protein with multiple biological functions. The extracellular portion of this protein consisted of 33 cadherin repeat sequences, 5 epidermal growth factor-like domains, and a G-layer associated domain. This report detailed a case of glomerular cystic disease caused by a mutation in the FAT1 gene, which was treated with the traditional Chinese medicine formula 'Shen Jiu Fang Modified'. This formula included Astragalus, Atractylodes, Poria, Angelica, Clematis, Silkworm, Hedyotis diffusa, Hibiscus leaf, among other ingredients, and aimed to invigorate the spleen and promote diuresis, as well as to nourish the kidneys and promote blood circulation. This case demonstrated the potential of traditional Chinese medicine in addressing rare kidney diseases, offering new insights for the diagnosis and treatment of similar complex cases.

  • Papers
    Hong LIN, Tian-le SHI, Yu-qiu ZHANG, Hong CAO
    Fudan University Journal of Medical Sciences. 2024, 51(03): 285-294. https://doi.org/10.3969/j.issn.1672-8467.2024.03.001

    Objective: To investigate the contribution of microglia in the basolateral amygdala (BLA) to pain hypersensitivity and pain-related aversion in knee-joint monoarthritis mice. Methods: A total of 61 mice were used for behavioral tests (14 mice in the control group and 47 mice in the model group), and other 6 mice were used for cell morphology (3 mice in each group). An animal model of knee-joint monoarthritis was established by injection of complete Freund's adjuvant (CFA) into the knee-joint cavity of mice. The von Frey and Hargreaves tests were used to examine mechanical allodynia and thermal hyperalgesia in mice, respectively. The place escape/avoidance paradigm test was used to examine pain-related aversion. Open field test and elevated plus maze test were used to examine anxiety-like behaviors in mice. Morphological changes of microglia in the BLA area after CFA injection were assessed by 3D reconstruction of microglia in the BLA brain region using immunofluorescence staining and Imaris software. Results: Compared with the control group, CFA-arthritic mice produced significant mechanical and thermal hyperalgesia in the ipsilateral hindpaw and maintained for at least 12 and 19 days, respectively. Meanwhile, CFA injection induced pain-related aversion and anxiety-like behaviors in mice, accompanied by significant activation of BLA microglia. Inhibition of BLA microglia activation alleviated CFA-induced hyperalgesia and aversive behaviors but had no significant effects on anxiety-like behaviors. Conclusion: CFA-arthritic mice produce hyperalgesia, pain-related aversion, and anxious behavior, in which hyperalgesia and pain-related aversion may be mediated by the activation of microglia in BLA.

  • Medical Experience Communications
    Zhe-yi FANG, Jin-yu LIU, Jia-yan HUANG
    Fudan University Journal of Medical Sciences. 2024, 51(02): 230-237. https://doi.org/10.3969/j.issn.1672-8467.2024.02.013

    Objective: To analyze the budget impact of a price increase for carotid endarterectomy (CEA) on the total expenditure of health insurance expenditure in China. Methods: We set 2021 as the base year, and 2022-2026 as the study years. A budget impact analysis model was developed to calculate the expenditure of health insurance funds over the next 5 years following a 30% price increase for carotid endarterectomy. Data on the target population, treatment costs, and market share changes both nationwide and in four sample cities were used. The data was collected in May to Jul 2022. Results: The price increase for carotid endarterectomy will reduce total health insurance fund expenditures nationwide by 143.176 2 million yuan over five years. Total health insurance fund expenditures in the sample cities will also decrease to varying degrees. The higher the price increase for the surgical procedure, the greater the decrease in total expenditure of the health insurance fund. The market share of the surgical procedure has the greatest impact on the total expenditure of the health insurance fund. Conclusion: Increasing the price of carotid endarterectomy may lead to increase in its market share and decline in the health insurance fund expenditures in future five years.

  • Medical Experience Communications
    Jie ZHU, Pei-qi FANG, Bai-shen PAN, Wei GUO, Bei-li WANG
    Fudan University Journal of Medical Sciences. 2024, 51(03): 368-377. https://doi.org/10.3969/j.issn.1672-8467.2024.03.011

    Objective: To investigate the role of the TNFRSF12A molecule in the pathogenesis of liver cancer. Methods: Through comprehensive analysis of the Cancer Genome Atlas Program (TCGA) database and single-cell sequencing data, we studied the expression of TNFRSF12A in liver cancer and its correlation with prognosis. HPA database was utilized to analyze the subcellular localization of TNFRSF12A, and GO and KEGG analyses were performed by DAVID. TIME 2.0 was employed to analyze the correlation between TNFRSF12A and immune cell infiltration in liver cancer tissues. Results: TNFRSF12A was found to be highly expressed in liver cancer tissues, significantly correlating with patient survival prognosis (OS: HR=1.61, P=0.007 0; RFS: HR=1.45, P=0.037 0;PFS: HR=1.30, P=0.099 0; DSS: HR=1.67, P=0.027 0), as well as age (P=0.046 7) and BCLC stage (P=0.045 6). TNFRSF12A co-expressed with tumor stem cell markers (CD24, SOX4, ANPEP), indicating a strong link to malignancy. Furthermore, molecular functional analysis unveiled that IL-2R primarily existed in the cell cytoplasm and played a role in processes such as cell apoptosis, invasion, and protein binding. Moreover, TNFRSF12A was associated with Treg cells and immune cell infiltration, further suggesting its role in tumor immune regulation. Conclusion: TNFRSF12A exhibits a significant elevation within liver tumors and shows a notable correlation with patients' prognosis. Tumor cells engage in interactions with cytokines produced by Tregs, thereby reshaping the tumor microenvironment. The potential clinical significance of TNFRSF12A as a prognostic marker for tumors holds promise in offering novel avenues for personalized treatment and prognosis prediction.

  • Reviews
    Jia-wei XIONG, Rui-qi MA, Hua-peng YU, Lin MOU, Xiao-fen MO
    Fudan University Journal of Medical Sciences. 2024, 51(04): 614-619. https://doi.org/10.3969/j.issn.1672-8467.2024.04.022

    Leonurine (SCM-198) was discovered as one of the active constituents of the Herba Leonuri (HL). Now it can be artificially synthesized. Several recent researches has proven that it exhibits anti-inflammatory effect in several systems in animal models and cell culture in vitro. The key mechanism involves downgrading the activity of nuclear transcription factor-κB (NF-κB), thereby inhibiting the phosphorylation of several signal pathways such as PI3K/Akt, MAPK, ERK, and JNK, or upregulating the activity of Nrf2 related pathways, resulting in downregulated expression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), IL-1β, IL-2, IL-6, IL-8, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), chemokines, adhesion molecules, etc. Owing to the advantages of high safety and efficiency, the ease of administration, as well as its effectiveness in many organs and systems, leonurine has a widely prospect for future research and clinical applications. This article reviews the progress in the fundamental research of leonurine in multiple inflammation-related disease, and it could be expect to offer new possibilities for the treatment of these disease.

  • Papers
    Ming-xia LI, Shu-hui HU, Shu-yi SHAO, Ying ZHANG
    Fudan University Journal of Medical Sciences. 2024, 51(02): 151-158, 165. https://doi.org/10.3969/j.issn.1672-8467.2024.02.002

    Objective: To obtain guiding recommendations for the development of fertility preservation in female patients of reproductive age, so as to promote the scientific, standardized and orderly implementation of fertility preservation work. Methods: A previous questionnaire survey was used to determine the preliminary recommendations, a modified Delphi method was used to invite 18 domestic experts of fertility preservation to conduct two rounds of expert consultation. Then we adjusted and summarized recommendations according to the results of the consultation. Results: Finally, 14 guiding recommendations for the development of fertility preservation in female patients of reproductive age were obtained according to the results of the Delphi consultation, including 5 recommendations at technical level, 5 recommendations at political level and 4 recommendations at educational level. At technical level, it was proposed to establish a standardized operation process; at political level, it was proposed to improve the relevant legislation of fertility preservation in China to protect the safety and interests of patients; at educational level, it was suggested to take various forms to promote the mass dissemination of fertility preservation knowledge. Conclusion: Guiding recommendations for fertility preservation in female patients of reproductive age can provide detailed and comprehensive guidance for promoting fertility preservation in female patients of reproductive age in Shanghai, and provide reference for carrying out fertility preservation in other regions.

  • Methods and Techniques
    Zhi-xian TANG, Zhen LI, Qiao GUO, Jia-qi HU, Xue WANG, Xu-feng YAO
    Fudan University Journal of Medical Sciences. 2024, 51(03): 396-403. https://doi.org/10.3969/j.issn.1672-8467.2024.03.015

    Objective: To achieve automatic segmentation of cell nuclei in gastrointestinal cancer pathological images by using a deep learning algorithm, so as to assist in the quantitative analysis of subsequent pathological images. Methods: A total of 59 patients with gastrointestinal cancer treated in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from Jan 2022 to Feb 2022, were selected as the research objects. Python and LabelMe were used for data anonymization, image segmentation, and region of interest annotation of patients' pathological images. A total of 944 pathological images were included, and 9 703 nuclei were annotated. Then, a new semantic segmentation model based on deep learning was constructed. The model introduced deformable attention transformer (DAT) to realize automatic, accurate and efficient segmentation of pathological image nuclei. Finally, multiple segmentation evaluation criteria are used to evaluate the model's performance. Results: The mean absolute error of the segmentation results of the model proposed in this paper was 0.112 6, and the dice coefficient (Dice) was 0.721 5. Its effect was significantly better than the U-net baseline model, and it was ahead of models such as ResU-net++, R2Unet and R2AttUnet. Moreover, the segmentation results were relatively stable with good generalization. Conclusion: The segmentation model established in this study can accurately identify and segment the nuclei in the pathological images, with good robustness and generalization, which is helpful to play an auxiliary diagnostic role in practical applications.

  • Papers
    Yu CHEN, Xiao-xia TIAN, Li ZHU
    Fudan University Journal of Medical Sciences. 2024, 51(03): 331-337. https://doi.org/10.3969/j.issn.1672-8467.2024.03.006

    Objective: To explore the experience of migraine in patients undergoing closure of patent foramen ovale, so as to develop targeted interventions for relieving patients' migraine and improving quality of life. Methods: It was a qualitative study. A total of 11 patients who experienced migraine, underwent closure of patent foramen ovale, and admitted to the Department of Cardiology, Zhongshan Hospital, Fudan University from Oct 2022 to Apr 2023 were selected. One-to-one, in-depth semi-structured interviews were conducted. The conventional content analysis was used for data analysis. Results: The migraine experience of patients undergoing closure of foramen ovale could be shown in 5 themes: migraines attacked varied; migraines brought serious physical and mental effects; migraines were dealt with in a variety of ways; patients had expectations for closure; professional support was needed. Conclusion: The experience of migraine in patients undergoing closure of patent foramen ovale varied and was long-lasting. Patients were unable to effectively deal with migraine which had great negative effects. Multidisciplinary pain clinics could be established. Health care professionals should provide patients with professional and personalized pain management, pay attention to the accompanying symptoms and the negative mood, and improve patients' awareness and management level of migraine.

  • Papers
    Yue YIN, Shen LUO, Ling QIU, Hui WANG, Yang LIU, Hao FENG, Bei-li WANG, Hua JIANG, Xin WU
    Fudan University Journal of Medical Sciences. 2024, 51(05): 643-649. https://doi.org/10.3969/j.issn.1672-8467.2024.05.001

    Objective: To investigate anxious and depressive emotions in patients underwent cervical cancer surgery and to analyze its influencing factors. Methods: A total of 304 patients who underwent primary cervical cancer surgery in Obstetrics and Gynecology Hospital, Fudan University from Oct 2018 to Jun 2021, were recruited to evaluate the clinical effect based on cervical cancer-patient reported outcome 137 scale (CC-PRO137 scale). This study focused on dimensions of depressive and anxious emotions within this scale and explored their influencing factors. Results: The average scores of their depressive and anxious emotions within half a year after surgery were 4.141±0.798 and 4.020±0.616, respectively; and the average scores of depressive and anxious emotions more than one year after surgery were 4.250±0.802 and 4.097±0.613, respectively. By using statistical methods including analysis of variance and t test, it was found that there were statistically significant differences in the scores of depression and anxiety among cervical cancer patients under different postoperative adjuvant treatments and at different postoperative time points (P < 0.05). However, there were no statistically significant differences in the scores of depression and anxiety among patients with different ages, surgical methods, and clinical stages of cervical cancer (P > 0.05). Conclusion: Patients underwent cervical cancer surgery may suffer varying degree of depressive and anxious emotions, and the main influencing factors are different adjuvant treatments and the length of time for postsurgical recovery. Medical practitioners should strengthen comfort and care for patients with cervical cancer, especially those who receive chemotherapy and radiotherapy treatments and are in the primary stage after the surgery. Formulating positive intervention measures can effectively reduce the psychological pain of patients and safeguard their physical and mental health.

  • Papers
    Xilifu Nuerbiya, Zhang-yan LI, Shu-fei ZANG, Gulisitan Aisikaer, Rui ZHANG, Yue LI, Xin-ming XU, Jun LIU
    Fudan University Journal of Medical Sciences. 2024, 51(03): 352-358. https://doi.org/10.3969/j.issn.1672-8467.2024.03.009

    Objective: To investigate the relationship between triglyceride-gluscose (TyG) index in early pregnancy and the delivery of small for gestational age infant (SGA) in patients with gestational diabetes mellitus (GDM). Methods: A total of 1 532 pregnant women from Shanghai Fifth People's Hospital and the Second People's Hospital of Kashgar Region, who were enrolled in the study between Jan 2018 and Jun 2023 and met the inclusion criteria, were categorized into the group with GDM (754 cases) and the group without GDM (778 cases) based on the results of the oral glucose tolerance test (OGTT) conducted at 24-28 weeks of pregnancy. Within the GDM group, patients were further categorized into 3 groups based on neonatal weight: SGA group, large for gestational age infant (LGA) group, and appropriate for gestational age infant (AGA) group. A Logistic regression model was used to analyze the independent influences on SGA delivery in patients with GDM to analyze the correlation between the TyG index and the occurrence of SGA. The predictive value of the TyG index in early pregnancy for SGA delivery in GDM patients was analyzed using ROC curves. Results: The TyG index in the SGA group of GDM patients was significantly lower than that in the LGA, AGA and control without GDM group (P < 0.05). Multifactorial logistic regression analysis revealed that the TyG index was independently correlated with the SGA in GDM patients (P < 0.05). The ROC curve analysis demonstrated a good predictive value of the TyG index in early gestation for SGA delivery in GDM patients (AUC=0.821, 95% CI: 0.763-0.879, P < 0.001). Conclusion: The TyG index in early pregnancy among GDM patients is independently correlated with the occurrence of SGA infants and has a good predictive value for SGA delivery in GDM patients.

  • Papers
    Huan WU, Ji JI, Min LU, Yi-chun NING, Zhao-xing SUN, Xiao-qiang DING, Xiao-fang YU
    Fudan University Journal of Medical Sciences. 2024, 51(04): 455-464, 483. https://doi.org/10.3969/j.issn.1672-8467.2024.04.002

    Objective: To investigate the role of magnesium ion (Mg2+) in cisplatin-induced acute kidney injury (Cis-AKI) in kidney organoids and HK-2 cells, as well as the potential mechanism. Methods: Initially, we utilized human-derived induced pluripotent stem cells (iPSCs) to construct kidney organoids, and then built a Cis-AKI model based on kidney organoids. HE staining was used to observe the structure of kidney organoids, and immunofluorescence staining was used to observe the localization of markers and the expression of cleaved caspase-3. qRT-PCR was conducted to detect mRNA levels of tubular and glomerular markers, as well as inflammatory factors. Subsequently, the kidney organoids were randomly divided into control group, cisplatin group (Cis group), and Mg2+ pretreatment group (Cis+Mg2+ group). CCK-8 and ATP content assays were employed to evaluate the cell viability of renal tubular epithelial cells. TUNEL staining was performed to detect the apoptosis of renal tubular epithelial cells. Western blot was utilized to detect the expression of apoptosis-associated proteins (Bcl-2, Bax, cleaved caspase-3) and organic cation transporter 2 (OCT2). Immunofluorescence was used to detect the localization and expression of OCT2. Results: On the 10th day, the tubular structure in kidney organoids was visible, with abundant expression of renal markers. Treatment with 10 μmol/L cisplatin resulted in structural damage to kidney organoids, significantly increased expression of cleaved caspase-3 and mRNA levels of inflammatory factors, and significantly decreased ATP content. Compared with the Cis group, the Cis+Mg2+ group showed increased ATP content in kidney organoids, reduced number of TUNEL-positive cells, significantly decreased expression of apoptosis-associated proteins, and significantly decreased expression of OCT2. However, there was no significant improvement in HK-2 cell viability, the number of TUNEL-positive cells, or apoptosis-associated proteins in the Cis+Mg2+ group, and HK-2 cells did not express OCT2. Conclusion: Kidney organoid is an ideal in vitro model to study the pathogenesis and treatment of Cis-AKI. Mg2+ pretreatment can significantly reduce the damage of kidney organoids induced by cisplatin, and the mechanism may be related to the downregulation of OCT2.

  • Papers
    Shuang-yi SUN, Xin-xin HE, Wen-tong CHEN, Bin LYU, Meng-xiao GE, Yu-meng GUO
    Fudan University Journal of Medical Sciences. 2024, 51(04): 473-483. https://doi.org/10.3969/j.issn.1672-8467.2024.04.004

    Objective: To establish a scoring model for predicting the prognosis and drug sensitivity of colorectal cancer (CRC) based on the expression of disulfidptosis-related genes by bioinformatics analyses combined with the validation with CRC patient-derived organoids (CRC-PDOs). Methods: NMF (non-negative Matrix Factorization) algorithm, Cox and LASSO regression analyses were used to identify disulfidptosis-related genes with predictive value for CRC prognosis, and disulfidptosis-related risk scoring formula was constructed. The differential genes and enrichment pathways among different clusters were analyzed by GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes). The sensitivity of the high/low-risk clusters of CRC patients to chemotherapy drugs was predicted using the GDSC database and validated using CRC-PDOs. Results: The results of NMF algorithm showed that CRC patients could be grouped into two clusters based on the disulfidptosis-related genes. COX regression analysis demonstrated that LRPPRC and SLC7A11 were the only two genes with significance to predict the prognosis of CRC patients (P=0.047, 0.033). Low expression of SLC7A11 or high expression of LRPPRC in tumors of CRC patients was significantly correlated with overall survival (OS) (P=0.004, 0.003). Based on LASSO regression analysis, the mortality risk scoring formula for disulfidptosis was as follows: Risk score=LRPPRC×(-0.670 5)+SLC7A11×0.311 2, and the GSE161158 dataset could be re-grouped into high-risk and low-risk clusters accordingly. There were 125 differentially expressed genes (DEGs) between the two clusters. According to the GO and KEGG results, the up-regulated genes in high-risk cluster were mainly enriched in immune regulation, such as leukocyte chemotaxis, granulocyte migration and toll-like receptor binding. Low-risk cluster was characterized by pathways associated with sulfide metabolism, such as sulfur compound transmembrane transporter activity. Based on the GDSC database, the expression level of SLC7A11 and LRPPRC could predict chemotherapy drug sensitivity. As a representative, the efficacy of chemotherapy drug (irinotecan) on inhibiting the growth of CRC-PDOs was shown to be linearly correlated with the relative gene expression levels of SLC7A11 and LRPPRC in CRC tissues of patients (P=0.007, 0.040). Conclusion: According to the results based on the bioinformatics analyses and drug sensitivity testing on CRC-PDOs, disulfidptosis risk score could predict the prognosis and drug sensitivity of CRC patients, with potential clinical application prospect.

  • Papers
    Zhen-hua ZHU, Ruo-lin MAO, Zhi-hong CHEN
    Fudan University Journal of Medical Sciences. 2024, 51(02): 172-180. https://doi.org/10.3969/j.issn.1672-8467.2024.02.005

    Objective: To compare the clinical characteristics, peripheral blood inflammatory cells and levels of oxidative stress indicators between severe asthma and non-severe asthma patients, analyze the effects of neutrophils and oxidative stress molecules on the severity of asthma, and build a biological model for early prediction of severe asthma. Methods: From Aug 2018 to Jul 2019, 67 adult patients with stable asthma in our hospital were enrolled in this study. The clinical characteristics, peripheral blood inflammatory cells and levels of oxidative stress indicators of severe asthma group and non-severe asthma group were compared. Single factor Logistic regression analysis was conducted on severe asthma to screen out the most important five variables. Multifactor Logistic regression analysis was further conducted to establish a prediction model for severe asthma. Results: There were 25 severe asthma patients in this cohort, who had a longer course of disease, more frequent acute attacks, poorer asthma control, higher peripheral neutrophils, more severe obstructive ventilation dysfunction, lower myeloperoxidase (MPO) level and higher superoxide dismutase (SOD) than non-severe asthma patients. The patients with higher peripheral blood neutrophil count or proportion were more likely to show severe asthma, more frequent acute attacks, and more obvious reduction of pulmonary ventilation function. A panel of biomarkers, centered on peripheral blood neutrophil count and oxidative stress indicators SOD, human 8-epi-prostaglandin F2α (8-iso-PGF2α), could build a model to predict severe asthma. Conclusion: There are significant differences in clinical characteristics, peripheral blood inflammatory cells, and oxidative stress index levels between severe asthma patients and non-severe asthma patients. In stable asthma patients, levels of neutrophils and oxidative stress indicators such as SOD had an impact on the severity of asthma. The prediction model of severe asthma established on this basis provides a new idea for early recognition of severe asthma.

  • Reviews
    Da-wei LIN, Xiao-chun ZHANG, Feng ZHANG, Wen-zhi PAN, Da-xin ZHOU
    Fudan University Journal of Medical Sciences. 2024, 51(02): 257-261. https://doi.org/10.3969/j.issn.1672-8467.2024.02.017

    Tricuspid regurgitation (TR) cases are widely distributed in China. Poor clinical drug efficacy, high surgical risk, and poor prognosis for right heart failure are found in patients with moderate or severe TR. In recent years, with the innovation of valve instruments and the development of technology, transcatheter tricuspid valve treatment could be a new choice for high-risk TR patients in surgery. Many TR animal models have emerged these years for the research of the mechanism of TR and for the clinical verification of instruments. Therefore, this review focuses on how to develop an animal model of TR and discusses the advantages and disadvantages of these techniques.

  • Medical Experience Communications
    Hao WANG, Wei WU, Hui-qing LU, Yong WANG, Hao ZHU, Jiang-nan WU, Yun ZHANG, Rong HU
    Fudan University Journal of Medical Sciences. 2024, 51(02): 218-224. https://doi.org/10.3969/j.issn.1672-8467.2024.02.011

    Objective: To study the effect of drinking carbohydrate drinks before cesarean section on mothers and neonates, and to explore the application value of drinking carbohydrate drinks before cesarean section. Methods: The clinical data of 206 singleton women who underwent selective cesarean section in Obstetrics and Gynecology Hospital, Fudan University from Jun 2020 to Jun 2021 were retrospectively studied. Patients were divided into enhanced recovery after delivery (ERAD)group and control group according to whether drinking carbohydrate drinks before cesarean section. A retrospective cohort study was conducted to analyze the effect of preoperative carb drinks on preoperative fluid supplementation, postoperative rehabilitation and neonatal prognosis. Results: Among patients who fasted for less than 12 hours, the ERAD group had a lower fluid supplementation rate and a smaller average fluid supplementation volume compared to the control group (P < 0.05). The ERAD group had a lower rate of prokinetic agent using after surgery (P < 0.05). Among women without a history of abdominal surgery, the ERAD group had less blood loss 24 hours after surgery (P < 0.05). There were no significant differences in postoperative fever rate, incidence of nausea and vomiting, time of first flatus, neonatal apgar score, exit observation room neonatal blood, and neonatal neonatal intensive care unit (NICU) admission rate between the two groups. Among newborns with high-risk factors for hypoglycemia, the ERAD group had lower enter observation room neonatal blood compared to the control group, and a higher incidence of hypoglycemia (P < 0.05). Conclusion: Oral intake of carbohydrate drinks before cesarean section may be beneficial in reducing fluid supplementation before elective cesarean section, promoting postoperative gastrointestinal function recovery, and reducing postoperative bleeding. However, it may be related to the occurrence of neonatal hypoglycemia.

  • Papers
    Biao-qian TANG, Bo-hao CHEN, Yi-yang LI, Han-qing LIU, Shu-qing XU, Shu-mei WANG
    Fudan University Journal of Medical Sciences. 2024, 51(02): 159-165. https://doi.org/10.3969/j.issn.1672-8467.2024.02.003

    Objective: An isotemporal substitution model was used to explore the associations between activities including 10 minutes per day of physical activity (PA), sedentary behavior (SB), and sleep (SLP), and depressive symptoms among vocational school students with and without depressive symptoms. Methods: Questionnaire survey was conducted on grade one to grade three students attending vocational schools in Shanghai and Jiangsu Province from Dec 2021 to Jan 2022. Fourteen schools were selected using the convenience cluster sampling method. The selected students were categorized into depressive symptoms group and non-depressive symptoms group according to the Centre for Epidemiologic Studies Depression Scale (CES-D) scores. Results: A total of 40 339 questionnaires were collected, of which 10 086 were able to clearly remember the time of physical activity in the past week, and 8 149 were valid after data cleaning. According to the valid questionnaires, 5 496 students (67.44%) were in the non-depressive symptoms group and 2 653 (32.56%) were in the depressive symptoms group. The mean age of the students were (16.70±1.19) years. In the non-depressive symptoms group, substituting moderate physical activity (MPA) for all the other behaviors was negatively associated with CES-D scores, while substituting vigorous physical activity (VPA) for MPA and SB was positively associated with CES-D scores. In the depressive symptoms group, substituting walking, SB, and SLP with MPA was negatively associated with CES-D scores, respectively. The associations of MPA substituted for walking, SB, and SLP with CES-D scores were much stronger in the depressive symptoms group than in the non-depressive symptoms group. Conclusion: The detection rate of depressive symptoms was high among vocational students. Substituting MPA for walking, SB, and SLP were negatively associated with CES-D scores, with a stronger association observed in the depressive symptoms group than in the non-depressive symptoms group.

  • Methods and Techniques
    Ming-ya LI, Xue-lin WANG, Ye WEI, Pei-hong YANG, Lei SUN
    Fudan University Journal of Medical Sciences. 2024, 51(02): 249-256. https://doi.org/10.3969/j.issn.1672-8467.2024.02.016

    Objective: To establish a mouse model of type Ⅰ tricho-hepato-enteric syndrome (THES) induced by Ttc37 deficiency. Methods: Ttc37 flox strain was established by site-specifically inserted loxP sites into Ttc37 gene via CRISPR/CAS9 technology. Ubiquitously expressed CAG-Cre was introduced for all-tissue removal of Ttc37 in Ttc37flox/flox; CAG-Cre mice. The knock-out effect was confirmed by fluorescence quantitative PCR and Western blot. Phenotypic evaluations were conducted in 8-week-old mice including hematoxylin-eosin staining of skin, spleen, liver, bladder, and gastrointestinal tract (GI), serum enzyme activity assay of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), measurement of serum hemoglobin level, and ELISA for IgG and IgM level upon antigen immunization. Results: Similar to type Ⅰ THES patients, Ttc37flox/flox; CAG-Cre mice exhibited impaired development of hair shaft, epidermis, B cell and eyes, while liver, GI, bladder and serum hemoglobin level seemed normal under unstressed condition. Conclusion: A novel mouse model of type Ⅰ THES was constructed successfully, which was applicable for pathological study.

  • Papers
    Xiao-tao YAN, Wen-jie GUO, Cai-fang SHEN, Zi-yi CUI, Jia-qian WU, Ling FANG, Yu-chen ZHAO, Chen-yu QIAN, Yan-qiu YU, Pin-pin ZHENG
    Fudan University Journal of Medical Sciences. 2024, 51(04): 465-472. https://doi.org/10.3969/j.issn.1672-8467.2024.04.003
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    Objective: To develop a health belief model (HBM) based adolescent alcohol-related cognition scale to measure adolescent alcohol-related cognition and test its reliability and validity. Methods: The adolescents' alcohol-related cognitive scale was developed based on HBM model. By using purposive sampling, three general high schools in Qingpu District, Shanghai were selected. One-third of the classes from grades 10 and 11 in each school were randomly selected, and the students from these classes were surveyed as the research subjects.Exploratory factor analysis and confirmatory factor analysis were used to analyze its reliability (internal consistency reliability and combination reliability) and validity (structural validity, convergent validity, discriminative validity and criterion validity). Results: A total of 970 questionnaires were collected, of which 948 were valid, with an effective rate of 97.7%. The adolescents' alcohol-related cognitive scale contained 22 items. Five common factors were extracted from exploratory factor analysis, including perceived susceptibility, perceived severity, perceived benefits, perceived obstacles, and self-efficacy. The cumulative variance contribution rate reached 83.89%. The results of confirmatory factor analysis confirmed the overall fit of the model. The average variance extracted value (AVE) of each dimension was greater than 0.5, and the convergent validity of the model was ideal. The AVE square root of each dimension of the scale was greater than its correlation coefficient, indicating good discrimination validity. Cronbach's α coefficient of the total volume table was 0.892, indicating good overall reliability. Conclusion: The adolescents' alcohol-related cognitive scale developed in this study has good reliability and validity, which can be used to measure adolescents' alcohol-related perceptions.

  • Review
    Jing-yu TAN, Yan ZHANG, Jun CHEN, Dan-ni YANG, Yi-xin ZOU, Wan-shui YANG, Yong-bing XIANG
    Fudan University Journal of Medical Sciences. 2024, 51(03): 404-414. https://doi.org/10.3969/j.issn.1672-8467.2024.03.016

    The inflammatory effect of dietary is strongly related to the development of cancer, therefore, the diet-related inflammatory index was developed as a methodological tool to investigate the relationship between dietary, inflammation and tumors. In this paper, we summarized the results on diet-related inflammatory indices and common cancers of the digestive system based on relevant cancer epidemiological studies. The available epidemiological evidence suggests that pro-inflammatory diet is associated with an increased risk of gastrointestinal malignancies, with the strongest association with colorectal cancer, followed by esophageal and gastric cancers, and then pancreatic cancer, and the least evidence of studies with liver cancer. Among these studies, the level of evidence for esophageal cancer is lower than colorectal cancer, the study of gastric cancer has gender differences and problems in adjusting for confounders, and the study of pancreatic cancer has heterogeneous results. In view of the current research progress and deficiencies, prospective studies or population-based cohort studies, as well as strengthening nutritional epidemiological studies related to common tumors such as liver cancer could be considered in the future. This review is expecting to provide basic information and scientific basis for strengthening the related healthy eating behavior promotion in the prevention and control of digestive system tumors.

  • Papers
    Xiao-run CHEN, Li LUO, Jia-yan HUANG
    Fudan University Journal of Medical Sciences. 2024, 51(04): 552-557. https://doi.org/10.3969/j.issn.1672-8467.2024.04.013

    Objective: To describe the epidemiological characteristics of falls among hospitalized elderly patients in Shanghai, to explore the external and self-factors that affect falls in the elderly, and to provide evidence for the elderly to prevent falls. Methods: All the injury cases collected from the hospital information system of a general hospital in Shanghai during 2020 and 2022 based on Haddon Model were taken as the research objects. The epidemiological characteristics were analyzed using constituent ratio, chi-square test and Logistic regression analysis. Results: Falls occured in 11 152 cases (11.63%) within 95 880 hospitalized elderly patients aged 65 years old and over. The ratio of males to females was 0.49∶1. Falls were more likely to occur in females and those who lived with children, and the place was mainly home/residential institutions. The time distribution showed the fewest occurrence in February. The mainly injured part was the trunk and limbs with the nature of fracture. Multiple regression analysis showed that compared to males, 65-75 years old, spring, married status and living with spouses, the risk factors of falls in elderly patients were female, older age, winter, not in marriage and living with children. Conclusion: The elderly have a high risk of falls, which is influenced by a combination of factors such as personal health, the natural environment, and social support. Comprehensive measures should be taken to identify and address the risk of falls in the elderly, including personal health promotion, home environment optimization, harmonious family atmosphere, professional medical support, and social collaboration, in order to achieve effective prevention and management.

  • Papers
    Min-na SHEN, Li ZHANG, Xin-ning CHEN, Fei HUANG, Chao-gang BAI, Li-meng CHEN, Hai-xiang PENG, Yan ZHOU, Bei-li WANG, Bai-shen PAN, Wei GUO
    Fudan University Journal of Medical Sciences. 2024, 51(02): 166-171. https://doi.org/10.3969/j.issn.1672-8467.2024.02.004

    Objective: To evaluate the value of high-throughput sequencing (HTS) data reanalysis that does not include ERBB2 copy number variation (CNV) analysis, in identifying ERBB2 amplification in patients with colorectal cancer. Methods: The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed. According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH), the number of chromosome 17 (Chr17) reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification. Suspected positive samples were screened according to thresholds and verified by digital PCR, IHC and FISH. Results: The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299 (0.239±0.192). Using 0.298(1.25 times the mean) as the threshold indicating ERBB2 amplification, the data of 163 samples were analyzed, of which 7 cases were suspected to be positive, and the ratio ranged from 0.302 to 0.853. Among them, 5 cases were determined to be positive by IHC and/or FISH, and 6 cases were confirmed to be positive by digital PCR. The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1, and the correlation was good (r2=0.909). Conclusion: The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.

  • Papers
    Qun YAN, Sha-sha BIAN, Min-feng SHU
    Fudan University Journal of Medical Sciences. 2024, 51(03): 295-305. https://doi.org/10.3969/j.issn.1672-8467.2024.03.002

    Objective: To investigate the impact of radiotherapy simulant Zeocin induced double-stranded RNA (dsRNA)on double-stranded RNA-dependent protein kinase (PKR) activation and explore its molecular mechanism in inhibiting the growth and migration of malignant gliomas. Methods: We employed scratch assays, colony formation assays, and CCK8 assays to assess the impact of Zeocin on glioma growth and migration inhibition. Western blot and RT-qPCR were employed to measure the expression levels of methyl-modifying enzymes in glioma cells. The J2 antibody was used to detect endogenous dsRNA in malignant glioma cells treated with Zeocin. Western blot was used to assess the phosphorylation levels of PKR and eukaryotic initiating factor 2α (eIF2α). Results: Zeocin significantly inhibited growth and migration of glioma cells; Zeocin treatment induced the production of endogenous dsRNA in malignant glioma cells; as the concentration of Zeocin increased, phosphorylated PKR and eIF2α protein level also significantly increased; Zeocin downregulated the total m6A level of glioma cells in a dose-dependent manner; Zeocin selectively downregulated the protein level of methylase METTL14;Zeocin had no effect on mRNA levels of m6A modifying enzymes. Conclusion: Zeocin probably triggered more dsRNA by downregulating the m6A level of RNA in malignant glioma cells, which in turn activated the PKR/eIF2α pathway, ultimately leading to tumor growth inhibition.

  • Papers
    Hang CUI, Xiao-lei LIN
    Fudan University Journal of Medical Sciences. 2024, 51(04): 528-535. https://doi.org/10.3969/j.issn.1672-8467.2024.04.010

    Objective: To investigate the brain regions that play a key role in the impact of childhood adversity on cognitive function, based on the mediation effect analysis of debiased machine learning framework. Methods: The dataset, consisting of 460 volunteers, was randomly partitioned into a training set (n=368) and a validation set (n=92). To enhance the stability of the results, this study utilized a debiased machine learning mediation analysis method to develop models and draw conclusions from the training set, which were then validated with the validation set. Finally, the Bonferroni method was employed to correct for significance in the identified brain regions. Results: The experimental results for the training set and validation set were similar. The efficacy of the left superior parietal lobule was significant (validation set P < 0.001), exhibiting a positive effect (validation set Effect Size=0.78). The right frontopolar cortex, anterior cingulate cortex, and left inferior temporal gyrus were also significant (P < 0.001 for both training set and validation set) and were identified as having a negative effect in this process (validation set Effect Size =-0.037 and -0.034, respectively). The associations between the brain regions with significant effects and cognitive function are supported by existing literature. Conclusion: This study employed mediation analysis methods to investigate the mechanisms underlying the impact of childhood adversity on cognitive function. The results indicate that the left superior parietal lobule, right rostral anterior cingulate cortex, and left inferior temporal gyrus play crucial roles in the process of childhood adversity affecting cognitive function. Specifically, the left superior parietal lobule exhibits a positive effect, while the right rostral anterior cingulate cortex and left inferior temporal gyrus exhibit negative effects.

  • Case Reports
    Wen-ting JIN, Jia-yi NI, Bi-jie HU, Jue PAN
    Fudan University Journal of Medical Sciences. 2024, 51(02): 272-276. https://doi.org/10.3969/j.issn.1672-8467.2024.02.020

    With the increasing application of immune checkpoint inhibitors (ICI) in anti-tumor therapy, ICI related infections are often neglected. Mycobacterium tuberculosis (MTB) is also a common pathogen. We reported a case of ICI related pulmonary tuberculosis from Zhongshan Hospital, Fudan University. Meanwhile, 18 cases of ICI related tuberculosis infection were collected through literature search, and the characteristics of ICI related tuberculosis were analyzed to improve the understanding in clinic practice. All the cases were confirmed TB including 15 cases of pulmonary tuberculosis (1 case with complication of intestinal tuberculosis) and 4 cases of extra-pulmonary tuberculosis (1 case of disseminated tuberculosis, bone tuberculosis, tuberculous pericarditis and tuberculous pleurisy, respectively). The chest CT characteristics of pulmonary tuberculosis mainly included centrilobular nodules, ground glass nodules, empty lesions, patchy shadows, consolidation and large infiltration. Eighteen cases started anti-tuberculosis treatment, while 4 cases continued ICI treatment. Three cases suspended ICI (2 cases had remission after reuse) and 11 cases stopped ICI, and 1 case was not mentioned. ICI related tuberculosis may be a direct complication of tumor immunotherapy. It is necessary to screen tuberculosis infection and exclude active tuberculosis before immunotherapy. If there are suspected symptoms such as fever, cough and sputum during ICI treatment, active tuberculosis should be taken into account.

  • Papers
    Yu-jing ZHONG, Yi-ying WANG, Hai-ou LIU, Jia-qi LU
    Fudan University Journal of Medical Sciences. 2024, 51(06): 873-881. https://doi.org/10.3969/j.issn.1672-8467.2024.06.001

    Objective: To elucidate the potential mechanisms by which mesothelin (MSLN) contributes to chemotherapy resistance in high-grade serous ovarian cancer (HGSOC). Methods: A Meta-analysis utilizing public ovarian cancer databases was performed to evaluate the correlation between MSLN expression levels and overall survival (OS) in ovarian cancer patients. Pathway enrichment analysis was employed to identify key signaling pathways regulated by MSLN and their roles in chemotherapy resistance. Additionally, the TCGA-HGSOC database was analyzed to examine genomic features associated with MSLN-mediated chemotherapy resistance. To validate the biological function of MSLN in chemotherapy resistance, an intraperitoneal metastasis model was established using MSLN-knockdown ID8 ovarian cancer cells in mice. Results: Elevated MSLN expression was significantly associated with poor patient prognosis (HR: 1.42, 95%CI: 1.16-1.74). Differential gene expression and pathway enrichment analyses revealed that high MSLN expression upregulates resistance-associated genes and pathways involved in drug metabolism and DNA-binding signaling. Genomic association analysis showed a negative correlation between high MSLN expression and chromosomal instability features, specifically CX3, CX11, and CX13 scores. In vivo studies demonstrated that MSLN knockdown enhanced the tumor-suppressive effects of cisplatin. Conclusion: High MSLN expression represents a potential biomarker for poor prognosis and chemotherapy resistance in HGSOC patients, suggesting MSLN as a promising target for therapeutic intervention.

  • Reviews
    Zhi-yun XUE, Bin LI, Xiu-ying CHEN
    Fudan University Journal of Medical Sciences. 2024, 51(05): 820-824. https://doi.org/10.3969/j.issn.1672-8467.2024.05.026

    The incidence of premature ovarian insufficiency (POI) is increasing and showing a trend of affecting younger women, which not only affects women's fertility, but also has the risk of low estrogen in the short and long term. The etiology of POI is complex and highly heterogeneous, including genetic factors, iatrogenic factors, autoimmune dysfunction, infection and environmental factors, but idiopathic POI still accounts for the majority. A lot of researches have focused on the correlation between autoimmune diseases and POI, among which autoimmune thyroid disease (AITD) plays an important role. Therefore, this article will review the current status of POI, the possible pathogenesis of AITD and related treatment progress.

  • Papers
    Xiao-chun ZHANG, Jia-ning FAN, Li ZHU, Feng ZHANG, Da-wei LIN, Wan-ling WANG, Wen-zhi PAN, Da-xin ZHOU, Jun-bo GE
    Fudan University Journal of Medical Sciences. 2024, 51(04): 505-514. https://doi.org/10.3969/j.issn.1672-8467.2024.04.007

    Objective: To investigate the clinical characteristics of female migraine patients with patent foramen ovale (PFO) and design a risk prediction model for PFO in female migraine patients (migraineur patients PFO risk prediction model, MPRPM). Methods: Female migraine patients who visited Zhongshan Hospital, Fudan University from Jun 1, 2019 to Dec 31, 2022 were included. Preoperative information and follow-up results after discontinuation of medication were collected. Patients were divided into PFO-positive and PFO-negative groups based on transesophageal echocardiography results. A multivariate Logistic regression model and a random forest model were constructed, and the random forest model was validated multidimensionally. Key features were selected based on the mean decrease accuracy (MDA) to construct MPRPM. Results: A total of 305 female patients were included in the study, with 204 patients in the PFO-positive group and 101 patients in the PFO-negative group. Multivariate Logistic regression analysis showed that age at migraine onset, attack frequency, severe impact on life during attacks, exercise-related headaches, menstruation-induced headaches, aura migraines, and a history of cryptogenic stroke were predictive factors for PFO positivity. The random forest model effectively predicted the incidence of PFO in female migraine patients, with an AUC of 0.895 (95%CI: 0.847-0.943). MPRPM demonstrated a sensitivity of 71.6% and specificity of 91.1% (AUC: 0.862, 95%CI: 0.818-0.906, P < 0.001). The optimal cut-off value was 2.5 points. Patients correctly classified by the model showed a higher rate of symptom improvement compared to incorrectly classified patients (94.3%vs. 82.0%, P=0.023). Conclusion: We identified predictive factors for PFO in migraine patients. MPRPM can provide guidance in the diagnostic process and therapeutic decision-making for female migraine patients, assist in patient triage, and reduce the healthcare burden.

  • Papers
    Qing LI, Hong-wei ZHANG, Li-mei CHEN, Qing CONG, Qing WANG, Long SUI, Ke-qin HUA
    Fudan University Journal of Medical Sciences. 2024, 51(05): 677-683. https://doi.org/10.3969/j.issn.1672-8467.2024.05.005

    Objective: To compare the clinical efficacy and pregnancy outcomes of CO2 laser and loop electrosurgical excision procedure (LEEP) surgery in the treatment of cervical high-grade squamous intraepithelial lesion (HSIL)in women of childbearing age. Methods: Patients with cervical HSIL of appropriate reproductive age (20-34 years old) who underwent satisfied colposcope, subsequently treated with laser or LEEP between Jan 2019 and Dec 2021 in Obstetrics and Gynecology Hospital, Fudan University were collected. All the patients were interpreted as transformation zone (TZ) type 1/2, and colposcopy biopsy diagnosed as cervical high-grade squamous intraepithelial lesion (HSIL) and received laser or LEEP according to the physician's advice and the patient's wishes.The effectiveness of the two surgeries was evaluated, and postoperative cytology, HPV result, and colposcopic pathology were compared. We monitored the surgical pregnancy rate, pregnancy complications, and pregnancy results after the surgery. Results: A total of 566 cases, including 233 laser cases and 333 LEEP cases, were enrolled. There was no significant difference between the two groups in terms of preoperative cytology, HPV distribution, or the length of cervical canal. After 6 months of surgery, 91.5% of patients who underwent laser therapy and 86.9% of those who underwent LEEP had normal cytology. The histology cure rate was 91.5% and the HPV conversion rate was 74.6% in both groups. The results of cytology, HPV, and colposcopic pathology had no significant difference between the two groups. The length of postoperative cervical canal was significantly longer in laser group than that in LEEP group [(29.09±3.15) mm vs. (27.05±3.84) mm, P < 0.001]. There was no statistically significant difference in postoperative pregnancy rate and pregnancy outcome between the two groups. Conclusion: Laser ablation and LEEP produce comparable effects pregnancy outcomes in cervical HSIL patients with TZ types 1 and 2, while LEEP has pathologic feedback, so its misdiagnosis of invasive cancer reduce.