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  • Reviews
    Zhi-xin YAN, Na-na SONG, Xiao-qiang DING
    Fudan University Journal of Medical Sciences. 2023, 50(05): 750-760. https://doi.org/10.3969/j.issn.1672-8467.2023.05.014

    Distribution of potassium ion (K+) among extracellular/intracellular fluid and subcellular organelles is in dynamic equilibrium under exquisite manipulation. K+ is most abundant in nuclei, which is followed by cytoplasmic matrix, mitochondria, endoplasmic reticulum and lysosome. Intracellular potassium homeostasis has great significance. It plays important roles in cell morphology maintenance, enzyme activities and energy metabolism modulation, biosynthesis of genetic material, cell proliferation and death, cell repair and migration, and immune response. Also, intracellular potassium disturbance is closely related to tumor, acute ischemic injuries, autoimmune diseases, endocrine diseases and neurodegenerative diseases. Correcting intracellular potassium disturbance has become a novel direction in clinical therapy. We give an overview of the current physiological condition, measuring techniques, regulation mechanisms and physiological/pathological significances of intracellular potassium homeostasis.

  • Papers
    Chinese Multidisciplinary Expert Task Force on Chronic Disease Management of TAK
    Fudan University Journal of Medical Sciences. 2023, 50(05): 633-654. https://doi.org/10.3969/j.issn.1672-8467.2023.05.001

    Takayasu arteritis (TAK) is a chronic autoimmune disease with the characteristics of early onset, long course, high disability rate and heavy disease burden, which seriously affects the physical and mental health and quality of life of patients. So far, there are no guidelines or expert consensus on the chronic disease management of TAK. Therefore, we have developmented the first domestic multidisciplinary recommendations on the chronic diseases management throughout the entire course of TAK, aiming to standardize the diagnosis and treatment process, improve the diagnosis and treatment level, and improve the prognosis of the disease for clinicians in relevant disciplines. The keypoints of this consensus include: (1) TAK has an early onset and high mortality rate. Early screening of the disease with a focus on middle-aged and young people with abnormal blood pressure, weakened or absent pulse, neck pain, or cervical vascular murmurs should be emphasized; (2) 2022 ACR/EULAR classification standard is recommended for the diagnosis of TAK; (3) The comprehensive assessment includes disease activity, vascular injury, important organ structures and functions related to vascular injury, disease risk, comorbidities, and quality of life; (4) Kerr score is recommended to assess disease activity; (5) A comprehensive vascular assessment is recommended, ultrasound, MRA, CTA, and PET/CT can all be used as imaging methods for the diagnosis and follow-up evaluation of TAK; (6) Wall thickening, T2 weighted high signal, and wall enhancement on MRA; appearance of thickening, enhancement, and low attenuation loops in the vascular wall on CTA; and an increase in SUV value of the wall on PET/CT, indicating wall inflammation; (7) In disease diagnosis and follow-up, the structure and function of important organs are recommended to be evaluated based on clinical manifestations, affected vascular sites, and severity; (8) The treatment of TAK should be dominated by the rheumatologists, and a "patient-centered" chronic disease management model should be established under a multidisciplinary diagnosis and treatment to achieve full course standardized treatment; (9) Glucocorticoids (GCs) are the basic medication for inducing remission, which should be combined with disease-modifying anti-rheumatic drugs (DMARDs) to achieve disease remission. Attention should be paid to drug efficacy and side effects; (10) Revascularization emphasizes the need for multidisciplinary teams (MDT) to negotiate and make decisions on the premise of stable disease control after sufficient anti-inflammatory treatment in the internal medicine department. Sequential internal medicine treatment and evaluation are still required after surgery; (11) Patients with pregnancy needs need to be comprehensively evaluated by the MDT to choose the appropriate timing of pregnancy, and closely monitored and followed up during pregnancy and childbirth; (12) Vaccination is best carried out during the stable period of the disease. During the use of glucocorticoids and DMARDs, inactivated vaccine can be inoculated, while live vaccine should be avoided; (13) Strengthen popular science promotion, improve the understanding, diagnosis and treatment level of TAK in relevant disciplines and grassroots medical workers, enhance patients' awareness and self-management ability of the disease, and implement a full lifecycle disease management model through tripartite collaboration between doctors, nurses, and patients.

  • Reviews
    Ting YI, Wen-li MI, Yan-qing WANG
    Fudan University Journal of Medical Sciences. 2023, 50(06): 919-927. https://doi.org/10.3969/j.issn.1672-8467.2023.06.017

    Itch is an unpleasant physical sensation that can cause scratching behavior. Chronic itch is a burdensome clinical problem of many skin diseases and some systemic diseases. Stubborn and severe itch seriously affects the physical and mental health as well as the quality of life of patients. It is important to use assortments of preclinical itch models to identify itch mechanisms, and to foster the development of better anti-pruritus drugs. In recent years, a variety of animal models of itch have been established, and advances have been made in basic itch research. The present study summarizes the commonly used mouse models in the research of itch and the frequently utilized behavioral evaluation for assessing the scratching, that provides a reference for the future itching and antipruritic research.

  • Reviews
    Jia-li ZHANG, Jia-man LIN, Huo-sheng QIANG, Hui YAN, Xin WANG, Ping XIANG
    Fudan University Journal of Medical Sciences. 2023, 50(05): 771-779. https://doi.org/10.3969/j.issn.1672-8467.2023.05.017

    Phosphine is a highly toxic gas. In recent years, the number of deaths caused by phosphine poisoning has been increasing, which poses a great threat to human safety. But so far, there is no specific antidote or first aid, diagnosis and treatment for phosphine poisoning. In this review, the physical and chemical properties of phosphine poisoning, poisoning background and symptoms, emergency treatment measures, combining the study of forensic toxicology mechanisms and detection methods, are analyzed to provide theoretical basis for the timely diagnosis and treatment of clinical patients suspected of phosphine poisoning.

  • Reviews
    Bing-jie WU, Ling-ying MA, Yi-jin XIANG, Wen ZHANG, Lin-di JIANG
    Fudan University Journal of Medical Sciences. 2023, 50(05): 761-764. https://doi.org/10.3969/j.issn.1672-8467.2023.05.015

    Takayasu arteritis (TAK) is a kind of chronic non-specific vasculitis. It is commonly treated with glucocorticoids, immunosuppressants and biologic and targeted agents. However, there are still problems of low disease remission rate and continuous progression of vascular lesions. In traditional Chinese medicine, TAK belongs to the category of "pulse bi". Traditional Chinese medicine played an irreplaceable role in relieving clinical symptoms, improving life quality and disease prognosis, and preventing recurrence. In this review, the authors summarized the pathogenesis, famous traditional Chinese medicine experts' theories and clinical experiences of TAK. The theory of reducing side effects and enhancing anti-inflammation effects was put forward. Based on the combination of different disease stages and syndromes, we integrated treatments of Chinese and western medicine of TAK, so as to form a new treatment model and strategy for improving long-term prognosis of TAK patients.

  • Case Report
    Yun-zhu ZHANG, Qing WANG, Ai ZHANG, Mei WANG, Ya-nan MAO, Yu-hua WANG
    Fudan University Journal of Medical Sciences. 2023, 50(05): 786-790. https://doi.org/10.3969/j.issn.1672-8467.2023.05.019

    Gastric-type endocervical adenocarcinoma (G-EAC) is the most common non-HPV-related cervical adenocarcinoma.The pathogenesis of the disease is currently unclear.G-EAC has a high degree of malignancy, and develops rapidly with non-specific clinical manifestations, hidden lesions and the poor prognosis.There is no relationship between G-EAC and HPV infection, therefore it's difficult to detect by routine cervical cancer screening, and it's easy to be misdiagnosed or never diagnosed.Compared with HPV-positive cervical cancer, the screening methods for this disease are limited, and early diagnosis is very difficult.In this paper, the diagnosis and treatment process of a G-EAC patient was reviewed, combined with literature review and Chinese expert consensus on the clinical diagnosis and treatment of G-EAC. The clinical manifestations and the current situation of diagnosis and treatment was analyzed, which indicates the importance of gynecological examination and tertiary diagnosis and treatment procedures.

  • Reviews
    Cao-jie LI, Jia-jun LI, Rong-xin CHEN
    Fudan University Journal of Medical Sciences. 2023, 50(06): 889-896. https://doi.org/10.3969/j.issn.1672-8467.2023.06.013

    Hepatocellular carcinoma is the fourth leading cause of cancer-related death worldwide. More than 80%-90% of hepatocellular carcinoma arises from hepatitis, liver fibrosis and cirrhosis. This review focuses on the impact of liver fibrosis on immune microenvironment. Liver fibrosis involving hepatic stellate cells, myofibroblasts, cancer-related fibroblasts and extracellular matrix affects innate and adaptive immunity through relevant pathways. An immunosuppressive microenvironment derived from liver fibrosis promotes the initiation and development of hepatocellular carcinoma.

  • Medical Experience Communications
    Qing LI, Li-mei CHEN, Hong-wei ZHANG, Shu-jun GAO, Qing WANG, Jun ZHANG, Long SUI
    Fudan University Journal of Medical Sciences. 2023, 50(05): 717-722. https://doi.org/10.3969/j.issn.1672-8467.2023.05.010

    Objective: To evaluate the clinical efficacy of FuFang ShaJiZiYou suppository in postmenopausal women before colposcopy. Methods: This was a prospective non-randomized non-blind clinical controlled study. A total of 204 postmenopausal patients requiring colposcopy from Obstetrics and Gynecology Hospital of Fudan University were enrolled. Combining doctor's suggestions and patient's wishes, the patients were divided into 4 groups according to whether vaginal medication was used or differernt type of medication before colposcopy: promestriene group (G1, 72 cases), estradiol cream group (G2, 13 cases), FuFang ShaJiZiYou suppository group (G3, 47 cases) and no medication group(G4, 72 cases). The general conditions, colposcopy scores of each group, and the coincidence rate between colposcopy diagnosis and postoperative pathology was compared. Results: The average medication time lasted 13.7 days in G1 group, 12.3 days in G2 group and 9.0 days in G3 group, respectively. The medication time in G3 group was significantly shorter than that in G1 group and G2 group (P < 0.001). Compared with G4 group, the application of promestriene, estradiol cream and FuFang ShaJiZiYou suppository had lower colposcopy score and more satisfactory colposcopy image. In addition, the colposcopy score in G2 group and G3 group were lower than that in G1 group, and the colposcopy image was more satisfactory (P < 0.001). There was no significant difference between colposcopic diagnosis and postoperative pathology in the 4 groups(P=0.846). Conclusion: The application of FuFang ShaJiZiYou suppository in postmenopausal women before colposcopy has the advantages of shorter medication time, lower medical cost, high satisfaction with colposcopy, and does not affect the coincidence rate between colposcopy diagnosis and postoperative pathology.

  • Papers
    Zi-kun TU, Ya-jing GAO, Xiao HAN, Hai-yan GUO, Yu-feng ZHOU
    Fudan University Journal of Medical Sciences. 2023, 50(06): 791-801. https://doi.org/10.3969/j.issn.1672-8467.2023.06.001

    Objective: To investigate whether macrophage pyroptosis is involved in the lung injury of bronchopulmonary dysplasia (BPD). Methods: Forty full-term newborn mice were divided into room air (RA) group and hyperoxia (HO) group (n=20 for each group). BPD mouse model was induced by chronic hyperoxia. Alveolarization was assessed by HE staining. Pulmonary vascular development was detected by CD31 immunohistochemistry. The degree of fibrosis was analyzed by Masson staining. The mRNA expression levels of pro-inflammatory cytokines and chemokines in lung tissue were quantified by qRT-PCR for Il6, Il1b, Mmp12, Ccl2, Ccl5 and Il8. Concentrations of IL-1β was detected by ELISA in serum and lung homogenates. The expressions of pyroptosis-associated proteins, NLRP3, Caspase-1 p20, N-gasdermin D (GSDMD) and mature IL-1β were evaluated by Western blot. The proportion of macrophages in bronchoalveolar lavage fluid was detected by flow cytometry. Immunofluorescence co-localization of F4/80 with NLRP3/Caspase-1/IL-1β was performed. AQP5 protein expression was analyzed by immunohistochemistry. Results: Compared with the RA group, alveolar block and pulmonary angiogenesis disorder were observed in the HO group, and pulmonary fibrosis was significantly increased. In lung tissue of HO group, the expression of pro-inflammatory cytokines was significantly up-regulated, the expression levels of pyroptosis-associated proteins were significantly increased; the levels of IL-1β in serum and lung homogenate were significantly increased; the proportion of macrophages in bronchoalveolar lavage fluid was significantly increased, and there was a significant immunofluorescence co-localization of F4/80 with NLRP3, Caspase-1 and IL-1β in lung tissue; AQP5-positive alveolar type Ⅰ epithelial cells were severely damaged. Conclusion: Hyperoxia-induced hyperactivation of the NLRP3/Caspase-1/GSDMD mediated pyroptosis may lead to lung injury in a hyperoxia-exposed BPD mouse model.

  • Medical Experience Communications
    ZHANG Xiao-chun, HOU Shi-qiang, LI Wei, CHEN Sha-sha, LI Ming-fei, ZHANG Lei, PAN Wen-zhi, ZHOU Da-xin, GE Jun-bo
    Objective To investigate the safety, efficacy and operational experience of the left atrial appendage occluder-WATCHMAN FLX for the first time in mainland China. Methods Patients with non-valvular atrial fibrillation who were admitted to the Department of Cardiology,Zhongshan Hospital Affiliated to Fudan University in May 2022 were screened. We completed echocardiography and CT evaluation before operation,and used WATCHMAN FLX system to complete transcatheter left atrial appendage occlusion (LAAO) under the guidance of transesophageal echocardiography and digital subtraction angiography (DSA), then evaluated the safety and immediate effectiveness,and summarized the operational experience. Results This occluder was used for the first time in mainland China,and a total of 4 operations were completed, of which 1 patient underwent LAAO alone, and the remaining 3 patients underwent "one-stop" of atrial fibrillation radiofrequency ablation combined with LAAO. There were no adverse events such as pericardial effusion, occluder displacement, occluder detachment, procedure-related embolism, bleeding, acute device-related thrombosis, or puncture site complications in all the patients. The success rate of immediate closure was 100%,3 cases had no residual shunt, and 1 case had a 1 mm residual shunt. Two new ways of FLX BALL were adopted for the deployment of the occluder:2 cases used the retraction method and 2 cases used the push method. The compression ratio range was 13%-28%, and the devices were not offensive. Conclusion The left atrial appendage occluder-WATCHMAN FLX has high safety and efficacy.
  • Papers
    Lin ZHU, Zheng KUAI, Le SONG, Yu HU, Xi-zhong SHEN, Dan-ying ZHANG
    Fudan University Journal of Medical Sciences. 2023, 50(06): 820-828. https://doi.org/10.3969/j.issn.1672-8467.2023.06.004

    Objective: To clear the intestinal commensal microbiota by using antibiotics in order to investigate the effect of commensal microbiota on atherosclerosis in ApoE-/- mice with different diets. Methods: The ApoE-/- mice were fed with normal chow diet and high-fat diet respectively, and antibiotics (vancomycin+metronidazole+neomycin sulfate+ampicillin) were used to intervene for 14 weeks. The formation of atherosclerotic plaques in the aorta of mice was evaluated by oil red O staining. The serum lipid metabolism and the levels of IL-1β, TNF-α and LPS were detected by ELISA. The expressions of inflammatory factors and tight junction proteins in the ileal and colonic epithelial cells of mice were also measured by Western blot and immunohistochemical staining. Results: With normal chow diet, the atherosclerotic plaques of mice increased significantly in the antibiotic intervention group (P=0.016). The levels of serum IL-1β and TNF-α in antibiotics group mice were significantly increased (P=0.005, P=0.021). The expressions of inflammatory factors IL-1β and TNF-α in ileal tissue of mice were significantly increased (P=0.003, P=0.007), and the expression of tight junction protein in intestinal tissue was significantly decreased (P < 0.050). With high-fat diet, the formation of atherosclerotic plaque of the mice in the antibiotic group were decreased (P=0.040); the serum total cholesterol level was decreased (P < 0.001), and the serum LPS level was also decreased (P=0.003). The expressions of inflammatory factors TNF-α (ileum: P=0.030, colon: P=0.029), IL-6 (ileum: P=0.040, colon: P=0.001) and IL-1β (ileum: P=0.004, colon: P=0.017) in intestinal tissue were significantly decreased, while the expression of tight junction protein in intestinal epithelial cells didn't change. Conclusion: The lack of intestinal commensal microbiota increases the level of systemic inflammation in ApoE-/- mice and promotes the formation of atherosclerotic plaque, which suggests that normal intestinal commensal bacteria may have a protective effect on atherosclerosis in ApoE-/- mice.

  • Case Reports
    ZHANG Yuan, LI Wei, PAN Cui-zhen, CHEN Dan-dan, CHEN Sha-sha, PAN Wen-zhi, LI Ming-fei, ZHANG Xiao-chun, ZHANG Lei, CHEN Hai-yan, KONG De-hong, GUO Ke-fang, SHU Xian-hong, ZHOU Da-xin, GE Jun-bo
    Severe tricuspid regurgitation (TR) is a common heart valve disease with high mortality. The guidelines recommend that interventional therapy is considerable for high-risk surgical patients. The existing devices for transcatheter tricuspid valve replacement (TTVR) are in the clinical researches. Echocardiography plays an important role in preoperative screening, intraoperative guiding, postoperative evaluation and follow-up. This manuscript reports a case with high risk of surgery was significantly improved after transjugular TTVR. The precautions of two-dimensional and three-dimensional transesophageal echocardiography (TEE) were analyzed to provide reference for clinical practice.
  • Methods and Techniques
    MENG Han-zhe, HE Wei-zhi, HU Lu-lu
    Objective To establish a step-by-step protocol of m6A-selective allyl chemical labeling and sequencing (m6A-SAC-seq) for detection of N6-methyladenosine (m6A) modifications of RNA at single nucleotide resolution level. Methods m6A-SAC-seq used specific methyltransferase MjDim1 to add allyl group to m6A, generating am6A. Then I2 was added to produce N1, N6-cyclized adenine (A) products. Mutations were introduced during reverse transcription to achieve single-nucleotide resolution detection. Methyltransferase MjDim1 was purified by HPLC. The conversion rate of m6A was calculated by probe and liquid chromatography-mass spectrometry (LC-MS/MS) to determine the activity of MjDim1 as quality control. Sample RNA was extracted and m6A sites were labeled with allyl group. The DNA library was constructed with m6A-sac-seq technology and sent for high-throughput sequencing. After sequencing, m6A sites were inferred via data analysis. The stoichiometry of m6A was calculated by standard curve calibration. Results After m6A-SAC-seq treatment, HIV reverse transcriptase recognized the cyclized am6A sites and introduced mutations during reverse transcription while the unmodified sites nearby remain unmutated. m6A sites could be identified by the specific mutation of A to T/C. Stoichiometry of m6A could be quantified by addition of spike-in probes and calibrating the mutation rate with the standard curve. Conclusion By using m6A-SAC-seq method,only 30 ng of mRNA or rRNA depleted total RNA samples and is capable to detect RNA m6A sites at single-nucleotide resolution.
  • Papers
    Hong-mei ZHENG, Ya-jin WEN, Xiao HAN, Rui FENG, Li-juan LIU, Ren-jie CHEN, Xiao-ling LI, Ting-ting JIN, Yu-feng ZHOU, Xiao-bo ZHANG
    Fudan University Journal of Medical Sciences. 2023, 50(05): 683-691. https://doi.org/10.3969/j.issn.1672-8467.2023.05.005

    Objective: To explore the profile of serum lipid metabolism in children with severe asthma and mild-to-moderate asthma, and investigate the potential plasma markers of children with severe asthma. Methods: Children with asthma from database of Children's Hospital, Fudan University were enrolled and divided into severe asthma group (n=50) and mild-to-moderate asthma group (n=54) during Sept 1, 2019 to Apr 30, 2021. Plasma from the children was collected to detect lipid molecules by the liquid chromatography-mass spectrometry (LC-MS) technique. Multivariate statistical analysis was used to compare the differences in lipid molecules between the two groups. The main disturbed metabolic pathways were analyzed by the KEGG database. The diagnostic value of significantly different lipid molecules for severe asthma was analyzed by the receiver operating characteristic (ROC) curve. Results: The average ages of severe asthma group and mild-to-moderate asthma group were (8.8±2.6) years and (8.4±2.8) years, respectively. There were no significant differences between the two groups in age and gender (P=0.075 and 0.422). Eosinophil percentage and eosinophil count were higher in the severe asthma group than in the mild-to-moderate asthma group. FEV1/FVC, %predicted FEF50, %predicted FEF75, %predicted MMEF were lower in the severe asthma group than those in the mild-to-moderate asthma group (P=0.003, 0.005, 0.005, 0.003 respectively). There were 39 different kinds of lipid molecules between the two groups. phosphatidylethanolamine (PE) (47∶10) and phosphatidylserine (PS) (40∶2) were the only two molecules with fold change (FC) > 1.5. KEGG metabolic pathway analysis showed that the differential metabolites participated in five metabolic pathways, including choline metabolism and glycerophospholipid metabolism. ROC curve showed the AUC values of clinical baseline variables combined with PE (47∶10) or with PS (40∶2) were 0.928 (95%CI: 0.851-1.000) and 0.923 (95%CI: 0.863-0.983), respectively, both higher than those of baseline module, which was 0.737 (95%CI: 0.640-0.834). Conclusion: Lipid metabolism was significantly altered in children with severe asthma, and 39 differential lipid molecules were identified, with the most significant disturbance in the choline metabolic pathway; PE (47∶10) and PS (40∶2) may be potential biomarkers for the diagnosis of severe asthma.

  • Methods and Techniques
    Yuan-chen HE, Chuan-rui SUN, Yin-zi CHEN, Xiao-wei CHEN, Xi-ling WANG
    Fudan University Journal of Medical Sciences. 2023, 50(05): 743-749, 760. https://doi.org/10.3969/j.issn.1672-8467.2023.05.013

    Objective: To construct a COVID-19 forecast model based on time-varying reproduction number and develop a visualization platform. Methods: The daily number of COVID-19 infections reported by Shanghai Municipal Health Commission was fitted into a Bayesian hierarchical model to estimate the time-varying reproduction number for the period of Mar 1 and Apr 29 and forecast the epidemic for the period of Apr 30 and May 6. The performance of forecast was assessed by randomised probability integral transform and ranked probability scoring. Data visualization platform was developed by Python, R, and other open resource software. Results: The time-varying reproduction number of the epidemic in Shanghai dropped below 1 on Apr 5 for the first time, and the model predicted that the "dynamic clearance" would be achieved in mid-late June. The probability distribution of the model forecasts and the observed values were statistically consistent (P=0.12) and had a good concentration (382.53±105.29). The visualization platform, which integrated the observed trend and the forecasted dynamics, was publicly available on Apr 19, 2022. Conclusion: The epidemic forecast model performed well. The visualization platform which fills the gap of in-depth data mining of COVID-19 in China can be quickly expanded to other cities with COVID-19 epidemic.

  • Papers
    YANG Shan-zhi, ZHANG Ying, QUAN Song-xia, HU Rui-min, YANG Yang, YANG Yu-meng, XING Guo-lan
    Objective To analyze the levels of components in complement system, in plasma and urine of diabetic kidney disease (DKD) patients, and their correlation with clinical, pathological features and prognosis. Methods The plasma and urine samples of 50 biopsy-diagnosed DKD patients (DKD group) and 50 cases of diabetic patients without no renal injury (DM group) and 50 cases of normal control groups were collected. Five complement components (factor H, factor B, factor P, C1q and C5a) were measured by enzyme-linked immunosorbent assay (ELISA).COX proportional hazard regression model was used to analyze the independent risk factors affecting renal prognosis, and ROC curve was drawn to analyze the value of factor B and C5a in predicting renal prognosis. Results In DKD patients, plasma levels of complement factor B, factor P, C1q and C5a were significantly higher than those in DM group and normal control subjects (P<0.05),factor H was lower than the healthy control group (P=0.03) and the DM group (P<0.001).Urine complement factor B, P factor and C5a were significantly higher than the healthy control group and the DM group (P<0.05), and factor H was lower than the healthy control group (P<0.001) and the DM group (P=0.008). There was no significant difference in the level of urinary C1q among the three groups. The levels of factor H, factor B, factor P and C5a were related to proteinuria, renal function and pathological changes of renal tissue. Multivariate Cox analysis showed that both urinary complement factor B (HR=2.63, 95% CI:1.377-5.023, P<0.001) and C5a (HR=1.33, 95%CI:1.06-1.668,P=0.014) were independent risk factors for renal prognosis. Conclusion In DKD patients, the alternative complement pathway is activated to varying degrees and is associated with proteinuria, renal histopathological changes, and poor renal prognosis. There was no significant correlation between the levels of classical complement pathway initiation factor C1q and the occurrence, development and prognosis of DKD.
  • Papers
    ZENG Ming-yao, CHEN Hong-ru, QI Chen-yang, ZHAO Zhong-hua, LI Fang, ZHANG Zhi-gang, WU Hui-juan
    Objective To investigate the correlation between YAP and podocytes apoptosis in focal segmental glomerulosclerosis (FSGS) and the role of YAP activator on the podocytes apoptosis.Methods The renal biopsy specimens of human FSGS were collected from the Nephrology Research Group of the Department of Pathology, School of Basic Medical Sciences, Fudan University. Adriamycin-induced FSGS mice model and Adriamycin-induced podocytes injury model in vitro were generated, and the above in vivo or in vitro model were treated in combination with YAP activator 1-Oleoyl lysophosphatidic acid (LPA). Immunohistochemistry (IHC) or double immunofluorescence staining, Western blot and Hoechst 33258 staining were used to examine the correlation between podocytes apoptosis and the expression of YAP in podocytes. Podocytes transfected with YAP siRNA were treated with LPA, and then YAP expression and podocytes apoptosis were examined.Results The more apoptotic podocytes, the more nuclear exclusion of YAP in FSGS were observed either in vivo or in vitro. YAP activator LPA improved glomerular morphology (t=17.68,P<0.000 1) and renal function(BUN:t=4.576,P=0.010 2;UACR:t=2.51,P=0.045 6) of Adriamycin-induced FSGS mice model, reduced the expression of p-YAP (S127), increased YAP nuclear entry and decreased podocyte apoptosis (P<0.001 for both expression of Cleaved Caspase-3 and Hoechst 33258 staining) induced by Adriamycin both in vivo and in vitro. RNA interference of YAP decreased both total and phosphorylated YAP expression, and increased podocytes apoptosis. LPA treatment decreased the expression of p-YAP (S127), promoted YAP nuclear localization and decreased the podocytes apoptosis (P<0.000 1 for both expression of Cleaved Caspase-3 and Hoechst 33258 staining) induced by YAP interference.Conclusion There are decrease in YAP activation, nuclear exclusion of YAP, and increased podocytes apoptosis in FSGS model. LPA can inhibit the phosphorylation of YAP at Ser127, promote its nuclear translocation, thus to protect podocytes from apoptosis to ameliorate the progression of FSGS.
  • Papers
    YAN Lei, TONG Chao-yang
    Objective To analyze the microarray expression data of sepsis-related acute respiratory distress syndrome (ARDS) in the Gene Expression Omnibus (GEO) database by bioinformatics methods.To observe the alterations of immune cells in peripheral blood, investigate differentially expressed genes (DEGs), and identify key genes in patients with sepsis related ARDS.Methods The data of sepsis-related ARDS patients were downloaded from GEO database GSE32707. CIBERSORT was applied to obtain a matrix of the content of 22 immune cells in peripheral blood of patients with sepsis and sepsis-related ARDS on day 0 and day 7. R software was used to analyze the DEGs of sepsis and sepsis-related ARDS patients on day 7, and gene ontology (GEO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to determine the important signaling pathways involved in ARDS. Hub genes were evaluated by protein interaction network.Results There was no significant difference in the distribution of immune cells between sepsis and sepsis-related ARDS on day 0, but on day 7, the proportion of CD8+T cells in peripheral blood of sepsis-related ARDS decreased significantly (P=0.009). The proportion of neutrophils was significantly increased (P=0.022). Seven core genes, RPL5EIF4A2RPL15EIF3ESRP9HSP90AA1, and RBM25, involved in the progression of sepsis-related ARDS.Conclusion With the progression of ARDS, the composition of peripheral blood immune cells in sepsis-related ARDS and the regulation of genes will change significantly, and seven hub genes may play an important role in this disease.
  • Papers
    Rui-xue XIA, Xiao-han ZHANG, Ya-jun HU, Bing ZHAO, Yi-ming LI, Min YU
    Fudan University Journal of Medical Sciences. 2023, 50(06): 802-809, 819. https://doi.org/10.3969/j.issn.1672-8467.2023.06.002

    Objective: To investigate the effect and mechanism of bromodomain containing 2 (Brd2) on mouse C2C12 myoblast differentiation. Methods: The expression of Brd2 in skeletal muscle tissues of muscular dystrophy patients was identified via Gene Expression Omnibus (GEO). Using differentiation medium that contained 2% horse serum to induce C2C12 myogenic differentiation, Brd2 protein level was detected by Western blot assay during the progression. Brd2 was knocked down or overexpressed in C2C12 cells by lentivirus-mediated transfection, cell morphological changes and protein levels of some differentiation markers were determined by immunofluorescence or Western blot assay during the differentiation process. Additionally, transcriptome sequence analysis and its related experiments were used to explore the possible regulatory signaling pathways of Brd2 in C2C12 myogenic differentiation. Results: Brd2 is low expressed in skeletal muscle of muscular dystrophy patients. In the process of inducing myogenic differentiation, Brd2 expression increased on day 2 and decreased on day 8. Knockdown of Brd2 inhibited the differentiation of myoblasts, while overexpression of Brd2 promoted the process. Wnt/β-catenin signaling pathway was regulated by Brd2. Conclusion: Brd2 promotes myogenic differentiation via Wnt/β-catenin signaling pathway, suggesting that Brd2 may be beneficial for skeletal muscle regeneration.

  • Methods and Techniques
    YANG Li-fan, PAN Wen-zhi, ZHANG Lei, ZHANG Xiao-chun, LI Ming-fei, LONG Yu-liang, GUAN Li-hua, ZHOU Da-xin, GE Jun-bo
    Objective Improvement in the way of atrial septum puncture (ASP) in order to operate more conveniently, decrease complications and make ASP more safe and effective.Methods ASP was performed in 28 Yorkshire swines under intra-cardiac echocardiography (ICE) guidance with the end of a SION guidewire of 0.014 inch.Statistical analyses of average pulmonary/systemic blood flow and average ASP time were performed using SPSS 22.0. We observed the closure of ASP 4 weeks after surgery.Results ASP was successfully performed in 28 Yorkshire swines without complications. Ultrasound cardiography showed left to right shunt through atrial septum after ASP. The average Qp/Qs ratio was 1.3±0.2 (median 1.3,95%CI:1.3-1.4). The average ASP time was (40.6±7.3) seconds (median 41 seconds,95%CI 37.8-43.3 seconds). Four weeks after surgery, the ASP holes in 28 swines were endothelialized and closed.Conclusion It is safe and efficient for ASP using the end of 0.014 inch SION guidewire under ICE guidance in Yorkshire swines.
  • Papers
    Yao ZHANG, Qing MIAO, Wen-ting JIN, Yu-yan MA, Meng-ran WANG, Bi-jie HU, Jue PAN
    Fudan University Journal of Medical Sciences. 2023, 50(05): 655-659, 682. https://doi.org/10.3969/j.issn.1672-8467.2023.05.002

    Objective: To summarize the clinical characteristics and outcomes of localized pulmonary infection by Scedosporium apiospermum (S. apiospermum) in order to provide evidence for diagnosis and treatment. Methods: We reviewed 8 patients diagnosed with S.apiospermum pulmonary infection from Jan 2018 to Dec 2021 at the department of infectious disease of Zhongshan Hospital, Fudan University. The clinical data, radiological findings, treatment and prognosis of the patients were analyzed retrospectively. Results: Among the 8 patients, there were 3 males and 5 females, with an average age of 58 (27-76) years. Identified by MALDI-TOF MS, 6 cases were S. apiospermum and 2 cases were S.boydii. There was 1 case had systemic sclerosis with pulmonary interstitial disease and diabetes, treated with Prednisone 10 mg/qd and Mycophenolate Mofetil 0.5 g/qd, 6 cases were accompanied by underlying pulmonary diseases, and 1 case had no underlying disease. The most common clinical symptoms were cough, followed by sputum production, haemoptysis, fever, dyspnea and weight loss. The mean BMI was 19.5 (15.6-23.2) kg/m2, and the BMI was less than 18.5 kg/m2 in 4 cases. The white blood cell counts, neutrophil counts and procalcitonin (PCT) were normal in all patients. The average value of erythrocyte sedimentation rate (ESR) and high sensitivity C-reactive protein (hs-CRP) were 32 mm/h (increased in 4 cases) and 24.8 mg/L (increased in 5 cases). G test and GM test were negative. The average CD4 lymphocyte count of patients was 512.8 (226.0-943.0) /μL, and the counts of 5 cases were < 500/μL. The chest CT findings were diverse: bronchiectasis (5 cases), nodules (3 cases), consolidation (3 cases), cavities (2 cases), pleural thickening (2 cases), and tree bud sign (2 cases), and various imaging findings often existed in combination. All the patients were treated with voriconazole, and 4 patients developed liver insufficient and visual hallucination after taking the medicine were stopped or adjusted to posaconazole. Follow up for 6 months after the start of treatment, the clinical symptoms of all patients were significantly improved. In imaging, 5 cases were absorbed, 2 cases were similar, and 1 case was deteriorated, which was considered to be caused by mycobacterium infection. Conclusion: The clinical and imaging manifestations of localized pulmonary infection by S. apiospermum are non-specific, inflammation markers ESR and hs-CRP are only slightly elevated, and the positive rates of G test and GM test are low, which make early diagnosis difficult. All the patients were treated with voriconazole and the overall prognosis is good.

  • Papers
    ROUZI Ainiwaer, HAN Lin-xiao, WU Yuan-yuan, ZHU Wen-si, LIU Jing, LIU Jin-guo, ZHOU Jian
    Objective To investigate the expression level and biological significance of aspartyl-tRNA synthetase 2,mitochondrial (DARS2) in non-small cell lung cancer (NSCLC). Methods DARS2 expression levels, prognostic value, clinicopathological staging correlation, mutation and methylation levels, and enrichment pathways in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC, were investigated using various databases. On this basis, the effect of DARS2 on the proliferation and migration ability of NSCLC cells was further analyzed by scratch assay and CCK-8 assay. Results GEPIA, GEO, and HPA database analysis results showed that DARS2 mRNA and protein expression levels were significantly upregulated in LUAD and LUSC, and DARS2 mRNA expression levels were positively correlated with pathological stage in LUAD. Survival analysis showed that patients with high DARS2 expression in LUAD had shorter survival times. cBioPortal analysis showed that DARS2 variability was 16% in LUAD and 18% in LUSC,respectively. UALCAN database methylation analysis showed that the methylation level of the DARS2 promoter region was significantly lower in LUAD and considerably higher in LUSC. Metascape database results showed that DARS2-related genes were highly enriched in both LUAD and LUSC, mainly in the cell cycle pathway. The results of scratch and CCK-8 assays showed that the knockdown of DARS2 significantly inhibited the proliferation and migration ability of H1299 cells. Conclusion DARS2 is overexpressed in LUAD and LUSC and may promote the proliferation and migration of NSCLC cells by participating in cell cycle regulation.
  • Methods and Techniques
    Yi-lin TANG, Lu-kai ZHANG, Liang JIN, Kun WANG, Yu-ling YANG, Zhuang-xuan MA, Cheng LI, Ming LI
    Fudan University Journal of Medical Sciences. 2023, 50(05): 723-730, 742. https://doi.org/10.3969/j.issn.1672-8467.2023.05.011

    Objective: To investigate the value of non-contrast CT 3D-radiomics based machine learning model for detecting aortic dissection (AD), and Stanford type A AD. Methods: A total of 128 patients who were suspected AD and underwent both thoracic and abdominal non-contrast and enhanced CT examination in Huadong Hospital, Fudan University between Jul 2011 and Jul 2022 were retrospectively enrolled. Radiologists made a diagnosis of AD based on the presentation of the enhanced CT images. The patients were randomly divided into the training set (n=89) and the validation set (n=39) in a 7∶3 ratio with simple random sampling. 3D slicer was used to manually delineate volumetric region of interest (VOI) on the non-contrast CT images. Pyradiomics was utilized to extract radiomics features from these images. The optimal feature set was selected using Spearman correlation coefficient and the least absolute shrinkage and selection operator (LASSO) algorithm. Subsequently, support vector machine (SVM), decision tree, random forest, eXtreme gradient boosting (XGBoost), light gradient boosting (LightGBM), and extra trees models were individually constructed based on this optimal feature set. The evaluation metrics included the area under the receiver operating characteristic curve (AUC), F1 score, accuracy, and recall. Results: In the training set, 35 radiomics features were selected, and based on these 35 features, the XGBoost model demonstrated the best performance in detecting AD. In the validation set, the XGBoost model achieved an AUC of 0.982, an F1 score of 0.960, an accuracy of 96.2%, and a recall of 100.0% in AD detection. Further for detecting Stanford type A AD, the optimal feature set consisted of 14 radiomic features in the training set. In the validation set, random forest model had the best performance, with the AUC of 0.852, F1 score of 0.625, accuracy of 76.9% and recall of 100.0%. Conclusion: The non-contrast CT 3D-radiomics based machine learning model is valuable in detecting AD and Stanford type A AD.

  • Papers
    Yu-wen ZHANG, Ying WANG, Zhao-hua XIN, Jia-lie FANG, Rui SONG, Hao-cen LI, Jia-wen KUANG, Yu-ting YANG, Jing-yi WANG
    Fudan University Journal of Medical Sciences. 2024, 51(01): 1-11. https://doi.org/10.3969/j.issn.1672-8467.2024.01.001

    Objective: To explore the severity of loneliness among the elderly in communities in Shanghai, and to identify factors associated with social and emotional loneliness respectively. Methods: A cross-sectional study was conducted in older adults aged 65 years or above in Pudong New Area, Jing'an District and Huangpu District in Shanghai from Mar to Jun 2021. In Pudong New Area, multi-stage stratified random sampling was conducted based on the age and gender distribution of Shanghai, while in Huangpu District and Jing'an District convenience sampling was conducted. A total of 635 samples were included in the study. Loneliness was assessed using the De Jong Gierveld Loneliness Scale with social and emotional loneliness subscales. Logistic regression analyses were conducted to identify factors associated with social and emotional loneliness. Results: Among the 635 participants, only 53 older adults (8.4%)were not lonely. Female (OR=0.46, 95%CI: 0.31-0.70), higher self-efficacy (OR=0.97, 95%CI: 0.94-1.00), more objective social support (OR=0.96, 95%CI: 0.93-0.99) were associated with less severe social loneliness. Meanwhile, higher level of education (secondary education, OR=0.56, 95%CI: 0.34-0.95; college or above, OR=0.30, 95%CI: 0.11-0.83) and higher self-efficacy (OR=0.96, 95%CI: 0.93-0.99) were associated with less severe emotional loneliness, while depression (OR=3.41, 95%CI: 1.76-6.60) and worse social capital (OR=2.02, 95%CI: 1.29-3.16) were associated with more severe emotional loneliness. Conclusion: Up to 91.6% of the elderly in our study sample were moderately lonely or above. The factors associated with social loneliness include self-efficacy, gender and social support. The factors associated with emotional loneliness are self-efficacy, education level, depression, and social capital.

  • Papers
    DONG Jing, SHANG Shuang, XIE Feng
    Objective To investigate the effect of ITGA5 on cervical cancer cell growth and invasion after RNA interference. Methods The expression of ITGA5 in cervical cancer and the effect on patient survival rates were analyzed by database TNMplot, Kaplan-Meier Plotter and Human Protein Atlas. RNA interference experiments were performed by using two specific siRNA sequences targeting ITGA5.The experiment was divided into three groups:siITGA5#1 interference group, siITGA5 # 2 interference group, and negative control group (non-specific siRNA).The mRNA and protein levels of ITGA5 in cervical cancer cells were measured by real-time quantitative PCR and Western blot, respectively, and HeLa and C-33A cells with high expression of endogenous ITGA5 were screened for subsequent experiments. ITGA5 levels in HeLa/C-33A cells after siRNA interference and the expression changes of c-Myc, BCL-2, Bax and Vimentin and E-cadherin were detected by Western blot. HeLa/C-33A cell proliferation was determined by CCK-8, apoptosis was measured by flow cytometry, cell invasion ability was assessed by the Transwell compartment invasion assay. Results Specific siRNA significantly downregulated ITGA5 protein expression in cervical cancer HeLa/C-33A cells when compared with negative controls; cervical cancer cell proliferation was significantly inhibited, while apoptosis increased (P<0.05), the expression of c-Myc and BCL-2 was decreased,while Bax was elevated. After interference with ITGA5, HeLa/C-33A cells showed a significantly reduced invasion capacity. Expression of the interstitial marker Vimentin was significantly suppressed, while E-cadherin (an epithelial cell marker) was significantly increased. Conclusion ITGA5 can significantly inhibit cervical cancer cell growth and invasion after RNA interference, and the effect of ITGA5 on the invasive ability of cervical cancer cells may be achieved by regulating interstilization of epithelial cells.
  • Reviews
    Ying-yu ZHANG, Xue-ling WANG, Lei-miao YIN
    Fudan University Journal of Medical Sciences. 2023, 50(05): 765-770. https://doi.org/10.3969/j.issn.1672-8467.2023.05.016

    Asthma is a complex respiratory disease with significant gender differences in incidence, morbidity symptoms and complications, yet the biological mechanisms leading to gender differences in asthma remain unclear. In this review, we systematized the gender differences in asthma with age based on the characteristics of asthma onset in male and female patients at different ages, and analyzed the possible potential biological mechanisms involved, in order to provide more options for gender-oriented asthma treatment.

  • Reviews
    Xiao-jiao WANG, Hong-yan LIU, Li-ping SUN, Hui MIN, Chun-yi GU
    Fudan University Journal of Medical Sciences. 2023, 50(05): 780-785, 790. https://doi.org/10.3969/j.issn.1672-8467.2023.05.018

    The appropriate weight gain during pregnancy has a critical impact on the short and long term health of both mother and child. The implementation of weight management strategies during pregnancy can help to reduce the risk of pregnancy complications and the maternal and fetal adverse events. However, it is difficult to carry out effective pregnancy weight management in clinical research. In this article, we reviewed the current standards, theoretical models, implementation paths and implementation contents of weight management during pregnancy, in order to provide a research basis for the development of weight management strategies for women in pregnancy in the future.

  • Papers
    HAO Meng-xin, NING Cheng-cheng, MA Feng-hua, ZHU Qin, TAO Xiang, LUO Xue-zhen, ZHANG Hong-wei, CHEN Xiao-jun
    Objective To evaluate the role of MRI-guided hysteroscopic precise one-step resection in the diagnosis of suspected myometrial invasion(MI) of endometrial cancer (EC) in patients desiring fertility preservation and the effects of suspected MI on the outcome of fertility-preserving treatment. Methods Sixty-five patients with early endometrial cancer who desiring fertility perservation were included, of which 41 myometrial infiltration patients were excluded by MRI imaging (reference group).EC patients with suspected MI on MRI (n=24) were prospectively enrolled and evaluated. Suspected MI was identified on MRI and resected via an en bloc resection technique (resecting the endometrial lesion, basal layer, and underneath myometrium en bloc) under hysteroscopy for pathological examination. Patients with negative pathological findings received progestin-based conservative therapy. The clinical characteristics and fertility-preserving outcomes of these patients were compared with those of patients without any evidence of MI on MRI. Results Through MRI-guided hysteroscopic one-step resection, 6 out of 24 patients were confirmed of myometrial invasion and included in the MI group for surgical treatment. Among patients with suspected MI on MRI, MI was pathologically excluded in 18 patients (non-MI group) with fertility-preserving treatment. The cumulative complete response rate were lower in the non-MI group than those in the reference group at the 8th month (27.8% vs. 61.0%,P=0.024) and the 18th month (82.5% vs. 94.8%,P=0.037) of follow-up. The cumulative recurrence rate of the Non-MI group after 12 months of CR was higher than that of the Reference group (50.0% vs. 0, P<0.001). All 3 Non-MI recurrent patients achieved complete remission after re-treatment. There was no statistical difference in pregnancy rate between the Non-MI group and the Reference group, with 1 successful pregnancy and full-term delivery in the Non-MI group. Conclusion The MRI-guided hysteroscopic precise one-step resection is an effective method for comprehensively evaluating the MI of early EC. Compared with MRI evaluation, it helps about 75% of patients preserve fertility, who need more careful treatment and more close follow-up.
  • Papers
    CHEN Xu-dong, ZHANG Qi, ZHANG Ying-lan, LIN Jia, WANG Feng, GUI Yi-ting, LIU Ting, LI Qiang
    Objective To explore and identify H3K27ac enriched non-conserved enhancers near human NPTX1, improve the annotation of NPTX1-related regulatory regions, and provide a corresponding theoretical basis for the study of NPTX1-related diseases and mutations in non-coding regions.Methods A total of 39 H3K27ac ChIP-seq data involving 7 tissues were downloaded from the CistromeDB database and analyzed. Peaks in the range of 100 kb on both sides of NPTX1 were selected. Fragments' sequence conservation among human, mouse and zebrafish was analyzed by ECR browser. The fragments were inserted into a dual luciferase validation vector, and dual luciferase assays were performed in human neural-derived cell line SH-SY5Y and human kidney-derived cell line 293T to detect enhancers' activity.Results We obtained 5 H3K27ac-enriched fragments. The DNA sequences of each fragment were not conserved among human, mouse and zebrafish. The ratio of dual luciferase activity of NPTX1-E1-P was significantly higher than that of the negative control in SH-SY5Y, but it was about 40% lower in 293T cells.Conclusion Among the H3K27ac-enriched fragments near NPTX1NPTX1-E1-P has enhancer activity in human neurogenic cell line SH-SY5Y,and low sequence conservation among species. Compared with the human neurogenic cell line SH-SY5Y,its enhancer activity is decreased in human kidney-derived cell line 293T.
  • Papers
    BEN Min-xi, ZHOU Bo-yan, LI Hui
    Objective To investigate the impact of race and its interaction with clinical factors on prognosis, and to determine whether racial factor is a key prognostic factor for melanoma.Methods We examined the effect of race on survival in melanoma with the Cox proportional hazards (CoxPH) model and two machine learning methods, random forest (RF) model and gradient boosting machine (GBM) model, using the Surveillance, Epidemiology, and End Results (SEER) database. A Logistic regression model was applied to investigate the interaction effects between race and stage/ulceration factors on the melanoma-specific mortality.Results Race showed borderline significance in the Cox model and had low variable importance in two machine learning models. In the Logistic regression model, for patients diagnosed at stage Ⅰ/Ⅱ, the odds ratios (OR) of melanoma-specific mortality in non-Hispanic blacks, non-Hispanic Asians, and Hispanics were 1.76 (95%CI: 1.34-2.31), 1.52 (95%CI: 1.16-1.99) and 1.19 (95%CI: 1.04-1.35) relative to whites, while the results were not significant for patients diagnosed at stage Ⅲ/Ⅳ.Conclusion Race is not an independent prognostic factor for melanoma. It is necessary to strengthen early screening and medical interventions for melanoma patients of non-white ethnicities.
  • Medical Experience Communications
    ZHOU Xue-hua, JIN Lin, SHEN Xia
    Objective To identify the relationship between hearing deprivation and social skills. Methods The mice were randomly divided into control group (n=36) and hearing deprivation group (n=32). On postnatal day 7 (P7), the experimental mice received one daily neomycin dose for 7 consecutive days (200 mg/kg, subcutaneous injection), and the corresponding dose of sterile saline was separately injected into the control group mice. The auditory brainstem response test (ABR) was applied to compare hearing thresholds of mice at the age of 1 month and 3 month. In mice at three months of age, three-chamber social interaction test was used to evaluate the social ability, Open field experiment was used to evaluate the anxiety level, and Y maze were used to evaluate the learning and memory function. Results Neomycin administration to mice in early period caused long lasting and severe hearing loss in adulthood. Compared with the controls, mice with hearing deprivation showed impaired social interaction capability[(64.89±9.58) s vs. (107.20±39.18) s,P<0.05) and social memory the hearing loss mice spent comparable time with strange mouse 1 and strange mouse 2[83.28(40.32-85.72) s vs. 57.48(45.56-64.36) s,P>0.05)] in the 3-chambered social test, elevated anxiety level in the open field test[157.00 (57.68-180.20) s vs. 202.50 (169.80-230.80) s,P<0.05),and impaired learning and memory function in the Y maze test (47.23%±11.81% vs. 61.28%±7.70%,P<0.05). Conclusion Our study demonstrated that hearing deprivation in early period in mice may lead to impaired social competence, elevated anxiety level and impaired learning and memory function. The findings support that hearing input is required for the development of hippocampal dependent normal cognitive function.
  • Papers
    Xin-yue GUO, Jia-huan PENG, Hui-lin XU, Yong-fu YU, Guo-you QIN
    Fudan University Journal of Medical Sciences. 2024, 51(01): 12-18. https://doi.org/10.3969/j.issn.1672-8467.2024.01.002

    Objective: To analyze the combined effect of body mass index (BMI) and age with cancer occurrence among a hypertensive population in Minhang District, Shanghai. Methods: Participants of this study were 212 394 hypertensive patients without cancer in Minhang District, Shanghai, registered in the electronic health information system from 2007 to 2015. Age and BMI were included as smoothing functions in the generalized additive Cox proportional risk model. The bivariate response model was constructed to visualize results using surface plots and to comprehensively analyze the association of BMI and age with the risk of cancer occurrence. Results: A total of 22 141 participants developed cancer by Dec 31, 2018. The association between age and the risk of cancer incidence showed an overall linear trend while the association between BMI and the risk of cancer incidence showed an overall "U" shape. BMI at about 26 kg/m2 showed the lowest risk of cancer incidence. The risk of cancer occurrence increased with increasing age in people with different BMIs. The associations between BMI and the risk of cancer incidence were different at different age groups: there was no significant association between BMI and the risk of cancer incidence in the young people (20-44 years). While in the middle-aged and older people aged over 45 years, BMI was associated with the risk of cancer incidence in a "U" shape. The lowest risk of cancer incidence was around the BMI of 26 kg/m2. Conclusion: BMI among the population with hypertension should be controlled in a reasonable range, especially in the middle-aged and older population, to prevent cancer occurrence.

  • Case Reports
    LI Lin-hui, ZHU Li, SHEN Zhi-hao
    Ankylosing spondylitis is a chronic inflammatory disease involving the spine. In the later stage, the patient can't lie flat. If combined with glottic tumor, the traditional straight supporting laryngoscope can't be used for surgery. Through the use of arc laryngoscope system, the vocal cord lesion resection of a patient with early glottic laryngeal cancer complicated with severe ankylosing spondylitis was successfully completed, and the tumor was successfully removed. There was no recurrence after 2 years of follow-up.
  • Reviews
    Yue-li DUAN, Xin-yu WANG
    Fudan University Journal of Medical Sciences. 2023, 50(06): 906-910, 927. https://doi.org/10.3969/j.issn.1672-8467.2023.06.015

    Monkeypox(MPX) is a zoonotic disease caused by monkeypox virus(MPXV), mostly self-limited and lacks specific drugs in the past. Since May 2022, there has been a remarkable increase in human monkeypox cases in different regions of the world. Some countries have used antiviral drugs against smallpox (such as tecovirimat, brincidofovir, cidofovir, etc.) and vaccinia immune globulin as MPX specific treatment drugs, mainly for severe and high-risk groups. Although smallpox vaccination may have a protective effect against MPXV and may improve clinical symptoms, the need for vaccination depends on the immune status of susceptible or exposed individuals, the risk of infection, the severity of infection that may occur, and availability of antiviral drugs to make a comprehensive decision. There are three smallpox vaccines currently available in different countries: JYNNEOSTM, ACAM2000® and Aventis Pasteur smallpox vaccine, the first two of which are currently recommended for MPX vaccination. Vaccination strategies include pre-exposure vaccination, post-exposure prophylaxis, and ring vaccination of close contacts. We reviewed the background knowledge, epidemiology, preventive treatment and other aspects of MPX, hoping to provide help for MPX prevention and emergency management.

  • Papers
    Yu QI, Hang WANG, Jian-ming GUO, Shuai JIANG
    Fudan University Journal of Medical Sciences. 2023, 50(06): 810-819. https://doi.org/10.3969/j.issn.1672-8467.2023.06.003

    Objective: To investigate the efficacy of intravesical Bacillus Calmette-Guérin (BCG) irrigation in the treatment of medium-risk and high-risk non-muscle-invasive bladder cancer (NMIBC), and to establish a predictive model with preoperative blood routine indexes in order to screen the patients who can gain benefit. Methods: A retrospective analysis was performed on 258 medium- and high-risk NMIBC patients admitted to the department of urology, Zhongshan Hospital, Fudan University from Jan 2014 to Jan 2019. All patients were treated with intravesical BCG injection after transurethral resection of bladder tumor (TURBT). The preoperative blood indexes and clinicopathological information of the patients were recorded. In the training set (n=180), LASSO regression and Cox multivariate regression models were used to screen prognostic factors in order to establish an efficacy predictive model. C-index was used to verify the predictive efficacy of the model, and the validation was carried out in the validation set (n=78). Results: All the 258 patients were followed up effectively, the median follow-up time was 53.0 months (12.0-98.2 months). The overall recurrence rate was 31.0% (80/258), the 1-year recurrence rate was 15.1% (39/258) and the 3-year recurrence rate was 25.6% (66/258). The screening of neutrophils, white blood cell and C-reactive protein (CRP) by LASSO regression could be used as prognostic factors. Multivariate Cox analysis showed that re-TURBT (P=0.001), age (> 70, P=0.008), CRP (P=0.002), and neutrophils (P=0.044) were independent predictors of the efficacy of BCG treatment. The C-index of the predictive model in the training set and the verification set were 0.744 and 0.847, respectively. Conclusion: Intravesical BCG irrigation is effective for the treatment of medium-risk and high-risk NMIBC. The established prognostic model (including neutrophils, CRP, age and re-TURBT) was more accurate in predicting the efficacy of intravesical BCG irrigation in non-muscular invasive bladder cancer.

  • Papers
    WANG Bei, ZHOU Guo-xia
    Objective To investigate spatial learning and memory and expression of phosphorylated cyclic AMP response element-binding protein (pCREB) and early growth response factor 1 (Egr1) in hippocampus of young mice anesthetized with Sevoflurane-nitrous oxide, compared with aged mice. Methods The mice aged 3 months (n=12) and 18 months (n=12) were randomly assigned to the experiment group and the control group, respectively, and there were 6 young mice and 6 old mice in each group. The mice in the experiment group were given 1.0 MAC sevoflurane, 70% N2O and 30% oxygen for 4 h, while mice in the control group were given 30% oxygen for 4 h. A 6-day acquisition training was conducted 48 h after exposure. The probe trial was conducted 24 h after training. Collecting hippocampal tissues 15 min after the probe trial and the expression of pCREB and Egr1 were assessed by Western blot and real-time quantitative PCR. Results There was no significant difference in spatial learning and memory as well as the expression of pCREB and Egr1 in hippocampus between the Sev+N2O group and the control group in young mice. In aged mice, the escape latency of the Sev+N2O group was significantly longer compared with the control group on day 4, 5 and 6 (P<0.05). The difference of the swimming speed between the two groups was not significant. During the spatial probe test, the percentage of distance and time in the target quadrant of the Sev+N2O group was significantly lower than that of the control group (P<0.01). The expression of pCREB and Egr1 in the hippocampus was significantly decreased compared with the control group (P<0.05). Conclusion Sevoflurane-nitrous oxide anesthesia did not impair spatial learning and memory of young mice, nor did it affect the expression of pCREB and Egr1 in hippocampus, but it did impair the aged mice.
  • Methods and Techniques
    Zi-yue CHEN, Shuai LIU, Wan-jie DU, Fang TONG, Yun-yun WANG, Ling-yang HUA, Ye GONG, Qing-jian HAN
    Fudan University Journal of Medical Sciences. 2023, 50(06): 869-880. https://doi.org/10.3969/j.issn.1672-8467.2023.06.011

    Objective: To develop a noninvasive method for expressing adeno-associated virus(AAV)in the peripheral nervous system to specifically manipulate ganglionic neurons. Methods: P0 mice were intraperitoneally injected 10 μL AAV2/9-EGFP with a viral titer of(2-5)×1012 vg/mL. When the mice were 2 months old,the tissues and organs were perfused and cut into slices. Immunofluorescence staining was performed on sections to observe the brightness and range of enhanced green fluorescent protein(EGFP)and determine the virus infection. Results: 69.11%±1.42% dorsal root ganglion(DRG)neurons,7.08%±1.16% trigeminal ganglion(TG)neurons,32.46%±1.81% nodose ganglion(NG)neurons,and 4.76%±0.29% sympathetic ganglion(SG)neurons were infected,while neurons in brain,spinal cord and internal organs were rarely infected. Conclusion: This method can specifically infect ganglionic neurons,but has extremely low efficiency in infecting glial cells,central nervous system neurons,or peripheral organs. It can be used to specifically manipulate ganglionic neurons.

  • Papers
    Xiu-hong CAO, Zhen-dong XU, Wei-min TAO, Rui-jing MA, Cui-cui QU, Yu-xiao DENG
    Fudan University Journal of Medical Sciences. 2023, 50(06): 842-848, 855. https://doi.org/10.3969/j.issn.1672-8467.2023.06.007

    Objective: To compare the predictive value of four different risk assessment models for postpartum venous thromboembolism(VTE). Methods: A retrospective study of the women who gave a birth in Shanghai First Maternal and Infant Health Hospital,Tongji University between Aug 2017 and Dec 2022 was conducted. A total of 255 parturients with VTE were included,and 765 parturients without VTE during the same period were randomly selected as control in a ratio of 1∶3. Four risk assessment models,Caprini Score,RCOG Guidline,Queensland Guideline and Shanghai Expert Consensus,were used respectively to score and classify the two groups of patients. The ROC curves were plotted to evaluate the predictive value of different models for puerperal venous thromboembolism. Classification of VTE patients by risk level and cumulative risk score in four risk assessment models were also made. Results: Maternal age,body mass index,and incidence of twin pregnancy,cesarean section,preterm birth,and preeclampsia were significantly higher in the thrombus group than in the control group(P<0.001). The AUCs of Caprini Score,RCOG Guideline,Queensland Guideline and Shanghai Expert Consensus were 0.676,0.763,0.782 and 0.767,respectively,and the difference was statistically significant(P<0.05). The Queensland Guideline identified more patients with thrombosis into high risk level. Conclusion: RCOG Guideline,Queensland Guideline and Shanghai Expert Consensus all have higher predictive value than Caprini Score,which are suitable for predicting and evaluating VTE in puerperal period. Queensland Guideline seems to have the highest accuracy.

  • Methods and Techniques
    Ying GU, Jing HU, Guo-ping LU, Yong-hao GUI, Bing SHEN, Wen-chao WANG, Yan-hong ZHANG, Ye CHENG, Yang CHEN, Xiao-di CAI, Hong XU, Rui FENG, Bo ZHANG, Xiao-bo ZHANG
    Fudan University Journal of Medical Sciences. 2023, 50(06): 881-888,896. https://doi.org/10.3969/j.issn.1672-8467.2023.06.012

    Objective: To construct a training program based on real clinical scenarios to enhance the emergency response ability of pediatric medical staff in Shanghai. Methods: We obtained the medical records of patients who entered the emergency room from Jan 2019 to Dec 2021 in the outpatient and emergency electronic medical record system of the Children’s Hospital of Fudan University,then extracted the names and specific contents of emergency diagnosis and treatment activities. We formed a list of entrustable professional activities(EPAs)for pediatric emergency rescue combined with expert interviews and Delphi method. Authoritative experts in the field of emergency rated the relevance and importance of trustworthy professional activities and content in pediatric emergency rescue. Based on the aforementioned work,a training program for improving the emergency rescue ability of pediatric medical staff had been formed,and experts in emergency medicine,nursing,management,and teaching related fields were then invited for two rounds of correspondence and expert argumentation. Results: The training program for improving the emergency rescue ability of pediatric medical staff included two core sections:theory and skills. Meanwhile,different training methods were set based on the course content. As proved by the experts,the program was in line with clinical reality,and had strong scientific and practical significance. Conclusion: The training program for improving the emergency rescue ability of pediatric medical staff was successfully constructed,it can provide reference for the implementation of targeted training in clinical practice to enhance the emergency first aid ability of pediatric emergency medical personnel.

  • Reviews
    Ying LIU, Li ZHANG, Ye-hong YANG
    Fudan University Journal of Medical Sciences. 2023, 50(06): 897-905. https://doi.org/10.3969/j.issn.1672-8467.2023.06.014

    Diabetes mellitus is a common chronic multisystemic disease in clinical practice. Long term chronic exposure to hyperglycaemia can damage the body's vascular system, eventually leading to microvascular complications such as diabetic nephropathy, diabetic retinopathy and diabetic neuropathy, which seriously affect the quality of life and life expectancy of patients. The intercellular cascade signal transductin system plays a key role in diabetic microangiopathy. Exosomes are exocrine vesicles with a diameter of 40-160 nm that are released from a variety of cells into the extracellular space. They can carry a variety of bioactive molecules such as nucleic acids, proteins and lipids, so as to complete the information transmission between cells. MicroRNA (miRNA) is a class of non-coding RNAs with a length of about 22 nucleotides, which can be encapsulated in vesicles to form exosomal miRNAs in exosomes. Exosome-delivered miRNAs in turn regulate phenotypic and functional changes in recipient cell functions. A number of studies have shown that exosomal miRNAs are key regulators of the occurrence and development of diabetic microvascular disease, and are expected to become diagnostic markers and therapeutic targets for diabetic microvascular complications. We summarized the worldwide researches on exosomal miRNAs in diabetic microvascular complications in recent years, hoping to provide new ideas for the study of exosomal miRNAs in diabetic microvascular complications.