1.Exosomal let-7a-5p derived from human umbilical cord mesenchymal stem cells alleviates coxsackievirus B3-induced cardiomyocyte ferroptosis via the SMAD2/ZFP36 signal axis
LI XIN ; HU YANAN ; WU YUETING ; YANG ZUOCHENG ; LIU YANG ; LIU HANMIN
Journal of Zhejiang University. Science. B 2024;25(5):422-437
Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and teenagers.However,its pathogenesis is still unclear,and effective treatments are lacking.This study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes(CMCs)induced by coxsackievirus B3(CVB3).CVB3 was utilized for inducing the VMC mouse model and cellular model.Cardiac echocardiography,left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)were implemented to assess the cardiac function.In CVB3-induced VMC mice,cardiac insufficiency was observed,as well as the altered levels of ferroptosis-related indicators(glutathione peroxidase 4(GPX4),glutathione(GSH),and malondialdehyde(MDA)).However,exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)could restore the changes caused by CVB3 stimulation.Let-7a-5p was enriched in hucMSCs-exo,and the inhibitory effect of hucMSCs-exolet-7a-5p mimic on CVB3-induced ferroptosis was higher than that of hucMSCs-exomimicNC(NC:negative control).Mothers against decapentaplegic homolog 2(SMAD2)increased in the VMC group,while the expression of zinc-finger protein 36(ZFP36)decreased.Let-7a-5p was confirmed to interact with SMAD2 messenger RNA(mRNA),and the SMAD2 protein interacted directly with the ZFP36 protein.Silencing SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related indicators.Meanwhile,the levels of GPX4,solute carrier family 7,member 11(SLC7A11),and GSH were lower in the SMAD2 overexpression plasmid(oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group,while those of MDA,reactive oxygen species(ROS),and Fe2+increased.In conclusion,these data showed that ferroptosis could be regulated by mediating SMAD2 expression.Exo-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36,which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.
2.Expression of FAT1 in Lung Adenocarcinoma and Its Relationship with Immune Cell Infiltration
DING CHEN ; ZHAO WENHAO ; HUANG HUA ; LI YONGWEN ; ZHANG ZHANRUI ; ZHANG RUIHAO ; WANG YANAN ; WU DI ; CHEN CHEN ; LIU HONGYU ; CHEN JUN
Chinese Journal of Lung Cancer 2024;27(2):109-117
Background and objective Lung cancer is a leading cause of cancer-related deaths.Non-small cell lung cancer(NSCLC)is the most common pathological subtype,with adenocarcinoma being the predominant type.FAT atypical cadherin 1(FAT1)is a receptor-like protein with a high frequency of mutations in lung adenocarcinoma.The protein encoded by FAT1 plays a crucial role in processes such as cell adhesion,proliferation,and differentiation.This study aims to investigate the expression of FAT1 in lung adenocarcinoma and its relationship with immune infiltration.Methods Gene expression levels and relevant clinical information of 513 lung adenocarcinoma samples and 397 adjacent lung samples were obtained through The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)data.The mRNA expression levels of the FAT1 gene in lung adenocarcinoma tissues were analyzed,along with its association with the prognosis of lung adenocarcinoma patients.Pathway enrichment analysis was conducted to explore the signaling pathways regulated by the FAT1 gene.Immu-noblotting was used to detect the differential expression of FAT1 in lung epithelial cells and various lung cancer cell lines,while immunohistochemistry was employed to assess FAT1 expression in lung cancer and adjacent tissues.Results FAT1 gene muta-tions were identified in 14%of lung adenocarcinoma patients.TCGA database data revealed significantly higher FAT1 mRNA expression in lung adenocarcinoma tissues compared to adjacent lung tissues.Kaplan-Meier analysis indicated lower survival rates in lung adenocarcinoma patients with higher FAT gene expression.Pathway enrichment analysis suggested the involve-ment of FAT1 in tumor development pathways,and its expression was closely associated with immune cell infiltration.Immu-nohistochemical validation demonstrated significantly higher expression of FAT1 in cancer tissues compared to adjacent lung tissues.Conclusion FAT1 mRNA is highly expressed in lung adenocarcinoma tissues,and elevated FAT1 mRNA expression is associated with poor prognosis in lung adenocarcinoma patients.FAT1 may serve as a potential biomarker for lung cancer.
3.Meta-synthesis of qualitative studies on self-disclosure in cancer patients
Di FU ; Ping JIANG ; Qun FAN ; Yanan LIU
Chinese Journal of Modern Nursing 2024;30(3):291-298
Objective:To integrate and systematically evaluate the self-disclosure experience and feelings of cancer patients.Methods:Qualitative studies on self-disclosure of cancer patients in PubMed, Web of Science, Cochrane Library, Embase, EBSCO, SinoMed, China National Knowledge Infrastructure, Wanfang Data, and VIP searched by computer from the establishment of the databases to March 8, 2023. The literature was evaluated using the authenticity evaluation tool of qualitative studies by the Joanna Briggs Institute Evidence-based Health Care, and the results were summarized in an aggregative integration approach.Results:A total of eight literatures were included, 30 main results were extracted, and similar results were summarized into ten new categories. Finally, two integrated results were composed, which were the promoting factors and the hindering factors of self-disclosure.Conclusions:Self-disclosure can enhance the intimate relationship between cancer patients and others, thereby improving the self-acceptance and mental health of cancer patients.
4.Diagnosis of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology
Lingyu LI ; Yun CAI ; Yanan CHEN ; Weiying DI
Chinese Journal of Neurology 2023;56(5):552-556
Endometrial carcinoma is one of common malignant tumors in female reproductive system, but it is extremely rare in leptomeningeal metastasis. The clinical manifestations and signs of meningeal carcinomatosis are complex and not specific. It is difficult to get a precise diagnosis early, and it has high rate of misdiagnosis and missed diagnosis. Accurate diagnosis and treatment of a case of leptomeningeal metastasis from endometrial carcinoma by next-generation sequencing and cerebrospinal fluid cytology are reported. The patient is an elderly female with a history of endometrial cancer. The main manifestations were fever, headache and dizziness; cerebrospinal fluid cytology showed tumor cells; AKT1 gene and TP53 gene were detected in endometrial carcinoma tissue, plasma and cerebrospinal fluid by next-generation sequencing. After treatment with intrathecal chemotherapy, immunotherapy combined with anti angiogenesis, the patient′s condition still progressed gradually and died finally. The purpose of this case report is to raise clinical awareness of recognition and treatment in early meningeal metastasis of endometrial carcinoma.
5.Clinical, genetic characteristics and follow-up in 14 patients with transthyretin familial amyloid polyneuropathy
Haoran LIU ; Yanan SUN ; Min XU ; Hai CHEN ; Li DI ; Jianying DUO ; Yuwei DA
Chinese Journal of Neurology 2023;56(6):673-678
Objective:To summarize the clinical and genetic characteristics in patients with transthyretin familial amyloid polyneuropathy (TTR-FAP).Methods:Fourteen unrelated TTR-FAP patients diagnosed at Xuanwu Hospital, Capital Medical University from September 2014 to February 2022 were retrospectively reviewed. The clinical manifestation, electrophysiology, cardiac function, biopsy and gene mutation were analyzed.Results:In the 14 patients (13 males, 1 female) diagnosed as TTR-FAP, the mean age at onset was 53.9 years (range: 33.0-71.0 years), with a mean course from symptom-onset to diagnosis of 4.1 years. The late-onset type occurred in 9 cases. Seven patients had a family history of TTR-FAP. Distal paresthesia of lower limbs was the commonest initial symptom (8 cases), with sensorimotor neuropathy and autonomic dysfunction seen initially in 4 and 2 cases, respectively. Cardiac involvement occurred in 6/8 of the patients. Nerve conduction studies indicated extremely axonal impairment with demyelinating features. Sural nerve biopsies showed moderate to severe axonal loss of myelinated fibers and the positive rate of Congo red staining was 8/14. Of 8 different TTR mutations detected, V50M was the most common (appearing in 5 cases). No obvious neuropathy progression was seen in the 5 patients who received tafamidis and 2 patients died of dyscrasia. Conclusions:TTR-FAP is more common in males, with sensorimotor axonal polyneuropathy, autonomic dysfunction and cardiac subclinical damage as the predominant symptoms. V50M is the commonest mutation. Tafamidis can delay the progression of disability.
6.Analysis of iodine nutrition status of children aged 8 - 10 and pregnant women in Fushun City, Liaoning Province in 2021
Fang PAN ; Yanan HU ; Huijie XIA ; Xinqing LIU ; Di GAO
Chinese Journal of Endemiology 2023;42(6):483-487
Objective:To study the iodine nutrition status of children aged 8 to 10 and pregnant women and thyroid of children in Fushun City, Liaoning Province, and to provide data for formulation of prevention and control programs on iodine deficiency disorders in Fushun.Methods:In 2021, according to population probability proportional sampling method (PPS), 1 street (township) was selected from 7 districts and counties (Dongzhou District, Wanghua District, Dongzhou District, Xinfu District, Fushun County, Xinbin County and Qingyuan County) in Fushun City according to 5 directions (east, south, west, north and middle) and 1 primary school was selected from each street (township). Forty to 50 children aged 8 to 10 from each primary school and 20 pregnant women were selected from each street (township). Urine samples and salt samples of children and pregnant women were collected for urine iodine and salt iodine levels detection, and thyroid gland of children was examined to calculate the goiter rate. Urine iodine was determined by "Determination of Iodine in Urine Part 1: Method for Determination of Iodine in Urine by As 3+-Ce 4+ Eatalytic Spectrophotometry", salt iodine was determined by "General Test Method in Salt Industry - Determination of Iodine", and children's thyroid was examined by Doppler B-ultrasound. Children iodine nutrition criteria: urinary iodine median < 100 μg/L was iodine deficiency; 100 - < 200 μg/L was suitable for iodine; 200 - < 300 μg/L was more than the appropriate amount of iodine; ≥300 μg/L was iodine excess. Pregnant women iodine nutrition criteria: urinary iodine median < 150 μg/L was iodine deficiency; 150 - < 250 μg/L was suitable for iodine. 250 - < 500 μg/L was more than the appropriate amount of iodine; ≥500 μg/L was iodine excess. Criteria for iodized salt: 18 - 33 mg/kg was qualified iodized salt; < 5 mg/kg was non-iodized salt; 5 - < 18 or > 33 mg/kg was unqualified iodized salt. Results:A total of 1 647 children aged 8 to 10 years were selected, including 829 males and 818 females. The median urinary iodine of children was 203.4 μg/L. The median urinary iodine of children by district and county ranged from 151.6 to 232.4 μg/L, and the difference was statistically significant ( H = 24.227, P < 0.001). A total of 700 urine samples were collected from pregnant women. The median urine iodine was 164.7 μg/L. The median urine iodine of pregnant women by district and county ranged from 131.3 to 193.0 μg/L, and the difference was statistically significant ( H = 48.516, P < 0.001). A total of 2 347 salt samples were collected, including 2 329 iodized salt samples, with iodized salt coverage rate of 99.23% (2 329/2 347). There were 2 254 qualified iodized salt samples, and the rate of qualified iodized salt was 96.04% (2 254/2 347). There was no correlation between total urinary iodine level and salt iodine content ( r = 0.129, P > 0.05). The thyroid gland of 1 439 children was examined, and 25 children of them had goiter, with an enlargement rate of 1.74% (25/1 439), lower than the national standard for elimination of iodine deficiency disorders (< 5%), and the difference between counties and districts was statistically significant (χ 2 = 31.692, P < 0.01). Conclusion:The iodine nutrition of 8 to 10 years old children and pregnant women in Fushun City, Liaoning Province in 2021 is basically at an appropriate level, the rate of qualified iodized salt is high, and the goiter rate of children conforms to the national elimination standards of iodine deficiency disorders.
7.Specific PCR Identification of Hibisci Cortex and Its Adulterants Based on DNA Signature Sequence Tags
Yanan LIU ; Zhongyi HUA ; Yuyang ZHAO ; Yan JIN ; Huangsheng PENG ; Chao JIANG ; Jingzhe PU ; Yuan YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(17):133-139
ObjectiveUncommon medicinal herbs are valuable medicinal resources, but their identification is a difficult problem in Chinese medicine due to their particularity and complexity. It is, therefore, urgent to establish a method for the identification of uncommon medicinal herbs. In this study, DNA signature sequence (DSS) tags were used to establish a specific polymerase chain reaction (PCR) identification method for Hibisci Cortex, the origin plant of Hibisci Cortex, and its adulterants. MethodThe candidate DSS tags were obtained from the chloroplast genome sequence analysis, and the DSS tags were verified by DNA sequencing. The specific identification primers for H. syriacus were designed based on the obtained reliable DSS tags. The PCR reaction conditions were optimized, and the tolerance and feasibility were investigated. ResultA DSS tag for identification of H. syriacus was obtained from the comparison of sequencing results of the amplified products with DSS, which revealed the distinguishing characteristics of Hibisci Cortex and its adulterants. A pair of specific primers for H. syriacus was designed according to the DSS tag. After PCR amplification and gel electrophoresis with the primers, a single bright band of about 270 bp was observed from H. syriacus, which did not appear in the four adulterants. ConclusionA DSS tag obtained in this study can be used to identify H. syriacus. The specific primers designed based on this DSS tag can accurately and simply identify the original plant of Hibisci Cortex and its adulterants, which provides a new method and idea for the molecular identification of genuine and counterfeit products of Hibisci Cortex.
8.Study of risk factors associated with prognosis in patients with aortic acute cerebral infarction
Na LIU ; Jianfa REN ; Weiying DI ; Yanan CHEN ; Yun CAI
Clinical Medicine of China 2022;38(6):521-526
Objective:To explore the risk factors associated with a three-month prognosis in patients with aortic acute cerebral infarction.Methods:A prospective study was conducted on 191 patients with aorthropathic acute cerebral infarction included in the Department of Neurology from June 2018 to December 2019, and the patients were divided into good prognosis group (153 cases) and poor prognosis group (38 cases) according to the MRS score of the patient's 3-month prognosis, and the general data, past medical history and blood pressure variability evaluation index (BPV) between the two groups were correlated analysis. The t-test was used to compare the measurement data with normal distribution, the χ 2 test was used to compare the counting data, and the Logistic regression analysis was used to analyze the risk factors. Results:The proportion of patients with diabetes history in the poor prognosis group (20.3% (31/153)), admission NIHSS score ((3.03±2.01) points), standard deviation (SD) ((12.06±4.46) mmHg) and coefficient of variation (CV) ((8.61±3.08)%) of systolic blood pressure at 24 h were lower than those in the good prognosis group (47.4% (18/38), (5.61±3.84) points, (14.75±3.46) mmHg, (10.41±2.18)%), the differences were statistically significant (the statistical values were χ 2=11.73, t=4.01, t=3.46, t=3.38; P values were 0.001, <0.001, 0.001, and 0.001, respectively). Because 24 h systolic blood pressure SD and 24 h systolic blood pressure CV had obvious collinearity, they were respectively included in the Logistic regression model. Taking diabetes history, NIHSS score and 24 h systolic blood pressure SD into the variables, the multivariate Logistic regression results of adverse prognostic risk factors in patients with acute cerebral infarction showed that the history of diabetes mellitus ( OR=3.649, 95% CI: 1.545-8.648, P=0.003), NIHSS score ( OR=1.472, 95% CI: 1.247-1.725, P<0.001) and 24 h systolic blood pressure SD ( OR=1.201, 95% CI: 1.085-1.336, P<0.001). Taking diabetes history, NIHSS score and 24 h systolic blood pressure CV into consideration, multivariate Logistic regression results of adverse prognostic risk factors in patients with acute cerebral infarction showed that the history of diabetes mellitus ( OR=4.695, 95% CI: 1.873-11.766, P=0.001), admission NIHSS score ( OR=1.922, 95% CI: 1.513-2.441, P<0.001) and 24 h systolic blood pressure CV ( OR=1.220, 95% CI: 1.045-1.425, P=0.012). All are independent risk factors influencing the prognosis of patients. Conclusion:The effect of 24 h systolic blood pressure SD and 24 h systolic blood pressure CV on patient prognosis was more valuable in clinical prediction, and the prognosis value of controlling blood glucose levels in patients with diabetes was higher in patients with cerebral infarction.
9.Diagnosis and treatment of free floating thrombus in carotid artery
Xueqiang FAN ; Jianbin ZHANG ; Zhiyong ZHOU ; Fei WANG ; Yuguang YANG ; Jianyan WEN ; Di LIU ; Jie CHEN ; Xia ZHENG ; Bo MA ; Yanan ZHEN ; Zhidong YE ; Peng LIU
Chinese Journal of General Surgery 2018;33(12):1007-1010
Objective To evaluate diagnostic method and treatment strategy for free floating thrombus in carotid artery.Methods From Ju12016 to Oct 2017,7 patients with free floating thrombus in carotid artery was diagnosed at our department.The medical history,symptoms,diagnosis,treatment strategy and prognosis of those patients were analyzed retrospectively.Results Among 7 patients,4 were symptomatic;4 patients were concomitant with severe carotid artery stenosis and 3 with mild to moderate stenosis.3 received carotid endarterectomy and patch angioplasty.4 received carotid artery stenting with distal cerebral protection divice.There was no perioperative and 30-day stroke,myocardial infarction,death or hyperperfusion syndrome occurred.The 12-month follow up showed no restenosis,no free floating thrombus recurrence and no ischemic cerebrovascular event.Conclusion Free floating filling defect in carotid artery is a typical sign for unstable plaque.Both carotid endarterectomy and carotid artery stenting can be used for the treatment of free floating thrombus.
10.Expression of HER2 in Colorectal Cancer and its Correlation With Prognosis
Likun LI ; Yanan DI ; Deyin PENG ; Yuhong ZHAO
Chinese Journal of Gastroenterology 2017;22(10):616-618
Background:Colorectal cancer (CRC)is a common malignant tumor in digestive system with high invasive and metastatic properties and has a high mortality rate. Human epidermal growth factor receptor 2 (HER2)is highly expressed in a variety of tumors and can inhibit tumor cell apoptosis. It is an indicator of poor prognosis in some malignancies. Aims:To study the expression of HER2 and its correlation with clinicopathological characteristics and prognosis of CRC. Methods:A total of 118 patients with CRC admitted from Feb. 2010 to Feb. 2011 consecutively at the Beijing Aerospace General Hospital were recruited. Expression level of HER2 protein in CRC tissue was determined immunohistochemically and its correlations with clinicopathological parameters and prognosis of CRC were analyzed. Results:Immunohisto-chemically,positive staining for HER2 was found in 41 cases of the CRC tissues (34. 7%),of which 18 (15. 3%)were strongly positive and 23 (19. 5%)were weakly positive. There were significant correlations between HER2 expression and depth of invasion,lymph node metastasis and TNM staging of CRC (P < 0. 05). Follow-up study revealed that the mortality rate increased with the increase of intensity of HER2 staining (P < 0. 05). Cox proportional hazard model confirmed that HER2 was an independent prognostic factor in CRC patients (RR = 2. 134,95% CI:1. 172-2. 415,P = 0. 006). Conclusions:High expression of HER2 is correlated with clinical staging and prognosis of CRC,and might be used as a biomarker for prediction of prognosis in CRC patients.

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