1.Phillygenin ameliorates tight junction proteins reduction, fibrosis, and apoptosis in mice with chronic colitis via TGR5-mediated PERK-eIF2α-Ca2+ pathway.
Huanhuan XUE ; Peijie LI ; Jing GUO ; Tinggui CHEN ; Shifei LI ; Liwei ZHANG
Journal of Pharmaceutical Analysis 2025;15(1):101042-101042
Ulcerative colitis (UC) is an idiopathic, relapsing, and etiologically complicated chronic inflammatory bowel disease. Despite substantial progress in the management of UC, the outcomes of mucosal barrier repair are unsatisfactory. In this study, phillygenin (PHI) treatment alleviated the symptoms of chronic colitis in mice, including body weight loss, severe disease activity index scores, colon shortening, splenomegaly, oxidative stress, and inflammatory response. In particular, PHI treatment ameliorated the tight junction proteins (TJs) reduction, fibrosis, apoptosis, and intestinal stem cell activity, indicating that PHI exerted beneficial effects on the intestinal mucosal barrier in mice with chronic colitis. In the NCM460 cells damage model, dextran sulfate sodium triggered the sequential induction of TJs reduction, fibrosis, and apoptosis. Takeda G protein-coupled receptor-5 (TGR5) dysfunction mediated NCM460 cell injury. Moreover, PHI treatment enhanced TJs and suppressed fibrosis and apoptosis to maintain NCM460 cell function, depending on TGR5 activation. PHI promoted TGR5 activation and elevated intracellular cyclic adenosine monophosphate levels in HEK 293T cells transfected with TGR5 expression plasmids. Cellular thermal shift assay and molecular docking studies confirmed that PHI directly binds to TGR5, indicating that PHI is an agonist of TGR5. The process of PERK-eIF2α pathway-mediated endoplasmic reticulum Ca2+ release was involved in NCM460 cell injury as well, which was associated with TGR5 dysfunction. When NCM460 cells were pretreated with PHI, the PERK-eIF2α pathway and elevated Ca2+ levels were blocked. In conclusion, our study demonstrated a novel mechanism that PHI inhibited the PERK-eIF2α-Ca2+ pathway through TGR5 activation to against DSS-induced TJs reduction, fibrosis, and apoptosis.
2.Screening and analysis of ferroptosis related genes in peripheral blood mononuclear cells of patients with systemic lupus erythematosus
Kang TAO ; Yuan TIAN ; Shifei LI ; Bing NI ; Xiaoqiang CHEN ; Zhifang ZHAI
Chinese Journal of Rheumatology 2024;28(2):93-98
Objective:To analyze the differentially expressed genes in PBMCs of patients with systemic lupus erythematosus (SLE) by bioinformatics methods screening and analyzing the key genes related to ferroptosis, and explore the possible mechanism of ferroptosis involved in the pathogenesis of SLE at the transcription level.Methods:The data sets and samples of healthy people (HC) and SLE patients who met the screening criteria were retrieved from the Gene Expression Omnibus (GEO), a sub-database of the National Center for Biotechnology Information (NCBI). The differentially expressed genes, GO enrichment analysis and KEGG pathway enrichment analysis were analyzed by GEO2R, R language and related software packages. The protein interaction network (PPI) of differential genes was analyzed by STRING, Cytoscape and other tools to explore the key genes and pathways. In addition, real-time quantitative reverse transcription PCR (RT-qPCR) was used to verify the expression of key genes. Mann-Whitney U test was used to compare the expression of key genes in PBMCs between the two groups. Spearman rank correlation analysis was used to explore the relationship between SLE disease activity and the level of key genes. Results:Six data sets were included in this study. A total of 166 genes related to ferroptosis were differentially expressed between SLE and HC groups. The differential genes were specifically expressed in alveolar macrophages, neutrophils, CD49 + cells and CD31 + cells. GO enrichment analysis and KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly involved in multiple signaling pathways closely related to SLE, such as oxidative stress response, infection and TNF signaling pathway. Hub genes screened by different algorithms all suggested RELA as a key gene, and RT-qPCR confirmed that compared with the RELA gene expression level in the HC group [0.75(0.37,1.13)], the expression level in SLE group [2.02 (1.19,4.06)] was increased, the difference was statistically significant ( Z=-3.08, P=0.002), and was positively correlated with the corresponding SLEDAI score of SLE samples ( r=0.52, P=0.019). Conclusion:The ferroptosis of many immune cells, including alveolar macrophages and CD49 + NK cells, is involved in the pathogenesis of SLE. RELA may be involved in the ferroptosis of PBMCs in SLE through the NF-κB pathway.
3.Changes in refractive power and ocular biometrics before and after the onset of myopia in children: the Anyang Childhood Eye Study
Menghai SHI ; Ying HUANG ; He LI ; Yongfang TU ; Lei LI ; Mengtian KANG ; Shifei WEI ; Yunyun SUN ; Lei YIN ; Ningli WANG ; Shiming LI
Chinese Journal of Experimental Ophthalmology 2024;42(5):453-461
Objective:To analyze the trends in refractive error and ocular biological parameters in elementary school students over 5 years, and to investigate the patterns of change before and after myopia onset.Methods:A cohort study was adopted.A total of 1 986 first-grade students from the Anyang Childhood Eye Study were enrolled in this cohort study and their right eye data were taken for analysis, including 1 126 boys and 860 girls.Every year, cycloplegic autorefraction was performed with 1% cyclopentolate eyedrops to obtain the spherical equivalent (SE).The axial length (AL), anterior chamber depth, lens thickness, mean corneal curvature (Km) and other parameters were obtained by ocular biometry.The lens refractive power (LP) was calculated using the Bennett formula.The subjects were assigned to persistent myopia group, non-myopia group and new onset myopia group.According to the age of myopia onset, the new onset myopia group was subdivided into the 8-, 9-, 10-, 11- and 12-year-old myopia groups to compare the differences in refractive error and ocular bioparameters among groups at different time points of follow-up.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2018-030).Written informed consent form was obtained from the guardians of each subject.Results:All children had a gradual SE drift toward myopia and a gradual increase in the AL with age, and there were significant differences in SE and AL between adjacent follow-up ages within the three groups (all at P<0.05).The earlier the onset of myopia, the higher the myopia SE and the longer the AL of the eye at the same follow-up age, the differences in SE between adjacent groups were statistically significant (all at P<0.05), and the differences in AL between adjacent groups at the follow-up age of 8 to 12 years were statistically significant (all at P<0.05).In the nonmyopia group, SE drifted toward emmetropia at a slow and steady rate of (-0.23±0.27)D/year, and AL also increased slowly and steadily at (0.18±0.13)mm/year.In the new onset myopia group, the changes in SE in the third, second, and first years before myopia onset were (-0.32±0.25), (-0.45±0.33), and (-0.98±0.44)D, and the increases in AL were (0.25±0.12), (0.32±0.15), and (0.48±0.19)mm, respectively.Both SE and AL change rates began to accelerate before myopia onset and slowed down after myopia onset, with statistically significant differences in the overall comparison of SE and AL change rates at different time intervals before and after myopia onset (all at P<0.001).The AL at myopia onset in boys was (24.11±0.70)mm, which was longer than (23.60±0.66)mm in girls ( t=159.71, P<0.01).LP decreased with age in all groups, with a faster rate before the age of 9 years and a slower rate after the age of 9 years.The mean decrease rate in LP was (-0.48±0.19), (-0.44±0.20), (-0.49±0.16), (-0.51±0.18), and (-0.48±0.19)D/year in the persistent myopia group and 8~11-year-old myopia group, respectively, which were significantly faster than -0.42±0.17 D/year in 12-year-old myopia group and (0.37±0.15)D/year in nonmyopia group (all at P<0.05).There was no statistically significant difference in Km among groups at different follow-up ages (all at P>0.05). Conclusions:The AL begins to grow at an accelerated rate 3 years before myopia onset, and the increase rate of the AL slows down after the onset of myopia, but it is still significantly faster than that of non-myopic children.In this process, the decrease in LP plays a compensatory role; there is no significant change in corneal curvature.The AL of males at the onset of myopia is longer than that of females at the same age.AL is an important indicator for the prevention and control of myopia.It is important to consider gender differences and to pay more attention to the growth rate when assessing AL.
4.Analysis of the diagnostic efficiency of wrist joint ulnar deviation supination 45° palmar oblique position for scaphoid waist fracture and displacement
Shifei CHEN ; Jun ZHANG ; Shuman HAN ; Wenjuan WU ; Zhiwei ZHONG ; Jing LI ; Zhe GUO ; Huizhao WU ; Ziyi QIAO
Journal of Practical Radiology 2024;40(5):805-808
Objective To investigate the clinical application value of wrist joint ulnar deviation supination 45° palmar oblique posi-tion in the diagnosis of scaphoid waist fracture and displacement.Methods The imaging and clinical data such as digital radiography(DR),CT of 93 wrist joint trauma patients were analyzed.The four position views including wrist joint anteroposterior+lateral view,scaphoid position,wrist joint ulnar deviation supination 45° palmar oblique position,scaphoid position+wrist joint ulnar devia-tion supination 45° palmar oblique position were analyzed by three readers.The consistency of the evaluation among different readers and the diagnostic efficiency of the diagnosis of scaphoid fracture and displacement were compared.Results The inter-observer agreement,sensitivity,specificity,accuracy,and other diagnostic efficiency of scaphoid waist fracture and displacement was evaluated,wrist joint ulnar deviation supination 45° palmar oblique position+scaphoid position and wrist joint ulnar deviation supination 45° palmar oblique position were better than those of scaphoid position and wrist joint anteroposterior+lateral view.The combination of wrist joint ulnar deviation supination 45° palmar oblique position+scaphoid position obtained the best diagnostic efficiency.Conclusion The wrist joint ulnar deviation supination 45° palmar oblique position shows the long axis of the scaphoid,which has a high diagnostic efficiency in the diagnosis of scaphoid waist fracture and displacement and would be used as a useful supplement to other scaphoid imaging.
5.Analysis of medical ethics review results in the Chinese Journal of Epidemiology from 2017 to 2020
Shifei WU ; Ying LI ; Jing ZHOU ; Yiyi ZHANG ; Yang LIU ; Xinying MA ; Miao HE
Chinese Journal of Endemiology 2023;42(10):852-856
Objective:To learn about the application of medical ethics review in scientific research and prevention of endemic diseases.Methods:The method of retrospective analysis was used, original articles on field epidemiological investigation and clinical medicines published by Chinese Journal of Epidemiology from 2017 to 2020 were collected. Examination of medical ethics in national, provincial and municipal fund programs and nonfund projects was carried out. Statistical analysis was performed using Cochran-Armitage trend test and Cochran-Mantel-Haenszel (CMH) test.Results:A total of 638 articles were collected from 2017 - 2020, with 36 excluded and 602 remaining. The proportion of papers published after medical ethics review over the past four years was 56.85% (83/146), 62.50% (105/168), 59.87% (94/157), and 60.31% (79/131), respectively. There was no statistically significant difference in trend testing ( Z = 0.41, P > 0.05). There was no statistically significant difference in the proportion of papers produced by academic works, on-site investigations, and clinical medicine programs among different years (χ 2 = 0.01, 1.31, 1.92, P > 0.05). The proportion of papers published that supported by various fund programs that had undergone medical ethics review over the past four years was 60.55% (66/109), 62.28%(71/114), 62.38% (63/101), and 60.22% (56/93), respectively. The trend test showed no statistically significant difference( Z = - 0.03, P > 0.05). There was no statistically significant difference in the proportion of papers published that supported by national level projects, provincial and ministerial level projects, and municipal level projects among different years (χ 2 = 0.06, 0.02, 0.19, P > 0.05). The difference in the trend test of the output papers of research projects approved by the higher-level ethics committee and marked with approval numbers over the past 4 years was statistically significant ( Z = 2.85, P < 0.01); the difference was statistically significant when compared across years (χ 2 = 8.13, P < 0.01); the proportion of papers increased from 8.22% (12/146) in 2017 to 18.08% (25/131) in 2020 (χ 2 = 7.04, P = 0.008). There was no statistically significant difference ( Z = - 0.53, P > 0.05) in the proportion of papers that expressed their consent in terms of informed consent over the past 4 years; There was no statistically significant difference in comparison between different years (χ 2 = 0.28, P > 0.05). Conclusions:Medical ethics review has been taken seriously by the majority of researchers and is widely used in endemic scientific research and prevention projects.
6.Analysis of the Symptoms of Jaundice Formula"Ma-Huang Lian-Yao Chi-Xiao-Dou Tang",Examination of Lian-Yao,and Insight into the Medicinal Value and Research of Forsythiae Fructus
Tao WANG ; Qilei CHEN ; Baifang WANG ; Jiankai TANG ; Xuejian GUO ; Shifei LI ; Hubiao CHEN ; Liwei ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(9):2909-2913
Ma-huang Lian-yao Chi-xiao-dou Tang is one of the three formulas for typhoid jaundice.But it has not received much attention,and the source of Lian-yao in the formula is unknown and the status and role are difficult to identify.In this paper,we first analyzed the functions of Ephedra and the symptoms of the whole formula.The formula was mainly used to"clear damp-heat"in order to remove jaundice.On this basis,it is proved that Lian-yao is the root of Forsythia,not"Qiao-gen".Today,the use of Forsythia instead of Lian-yao has the same effect.Then,the indispensable and important position of Forsythia in the formula was analyzed.It also pointed out some valuable directions for the medicinal use and research and development of Forsythia based on its wide range of effects but the lack of main symptoms.This paper provides insights for in-depth theoretical and practical research on Forsythiae Fructus.
7.Influencing factors for recompensation in patients with first-time decompensated hepatitis B cirrhosis
Jiajia RUAN ; Shifei WEN ; Xia WANG ; Li LI ; Juanjuan FU ; Xiucheng PAN
Journal of Clinical Hepatology 2022;38(8):1796-1800
Objective To investigate the influencing factors for recompensation in patients with first-time decompensated hepatitis B cirrhosis. Methods A total of 438 patients with first-time decompensated hepatitis B cirrhosis who attended The Affiliated Hospital of Xuzhou Medical University from September 1, 2011 to December 31, 2019 were enrolled, and all patients received comprehensive treatment including antiviral therapy. According to the outcome at the end of follow-up, the patients were divided into recompensation group and persistent decompensation group, and the independent influencing factors for recompensation were analyzed. Long-term survival rate was compared between the patients with different states of compensation. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data. A multivariate Cox proportional-hazards regression model analysis was used to investigate the influencing factors for recompensation. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison. Results Among the 438 patients with decompensated hepatitis B cirrhosis, 199 (45.4%) achieved recompensation after antiviral therapy. There were significant differences between the recompensation group and the persistent decompensation group in sustained virologic response (SVR) ( χ 2 =72.093, P < 0.001), single or multiple complications ( χ 2 =9.834, P =0.002), presence or absence of gastrointestinal bleeding ( χ 2 =6.346, P =0.012), serum creatinine (SCr) ( Z =-1.035, P =0.011), blood sodium concentration ( Z =-1.606, P =0.019), hemoglobin ( Z =1.455, P =0.006), and alanine aminotransferase (ALT) level ( Z =-2.194, P < 0.001). Baseline ALT level (odds ratio [ OR ]=1.002, 95% confidence interval [ CI ]: 1.000-1.003, P =0.009), SVR ( OR =5.760, 95% CI : 3.634-9.129, P < 0.001), and SCr ( OR =0.990, 95% CI : 0.981-1.000, P =0.047) were independent influencing factors for recompensation. The recompensation group had a significantly higher 5-year survival rate than the persistent decompensation group (87.9% vs 72.0%, χ 2 =9.886, P =0.025). Conclusion After comprehensive treatment, including antiviral therapy, approximately 45.4% of patients can achieve recompensation.Patients with elevated baseline ALT and achieved SVR were more likely to achieve recompensation, patients with elevated baseline serum creatinine had difficulty achieving recompensation, and patients with recompensation had a better long-term prognosis than patients with persistent decompensation.
8.Expressions and its prognostic value research of MMP-11 and cathepsin-D in gastric adenocarcinoma
Aidong LIU ; Shifei LIU ; Xudong SONG ; Luyang CHENG ; Hui TANG ; Yanjie XIONG ; Deyan LI ; Feng YAN ; Jianyang ZHAO ; Honghui GUO
Clinical Medicine of China 2019;35(1):22-25
Objective To detect the expressions of Matrix Metalloprotein-11 ( MMP-11 ) and Cathepsin-D(Cath-D),and investigate their relationship and prognostic significance. Methods The study included 95 cases′ clinical date and postoperative specimens of gastric adenocarcinoma ( North China University of Science and Technology Affiliated Hospital,2010. 01-2013. 12) as observation group,70 cases of normal gastric tissue(from observation group) as control group. Expressions of MMP-11 and Cath-D were detected by IHC methods in two groups. Results The positive rate of MMP-11 was 51. 6%( 49/95) in observation group,5. 7%(4/70)in control group(χ2=38. 884,P<0. 05). The positive rate of Cath-D was 73. 7%(70/95) in observation group,28. 6%(20/70) in control group(χ2=33. 082,P<0. 05). The positive rate of MMP-11 was correlated with metastasis and vascular invasion(χ2=7. 193、15. 566,P<0. 05). The positive rate of Cath-D was correlated with maximal diameter,lymph node metastasis,vascular invasion and proliferation index(χ2=7.431、5.654、6.569、6.801,P<0.05).There was positive relationship between MMP-11 and Cath-D in observation group(r=0. 46,P<0. 05). The expressions of MMP-11 and Cath-D were correlated with prognosis in gastric adenocarcinoma ( P<0. 05) . Conclusion The higher expressions and synergistic effect of MMP-11 and Cath-D may promote the occurrence and development in gastric adenocarcinoma. The joint detection of MMP-11 and Cath-D may be helpful to predict the prognosis of gastric adenocarcinoma.
9.Possibility of women treated with fertility-sparing surgery for non-epithelial ovarian tumors to safely and successfully become pregnant-a Chinese retrospective cohort study among 148 cases.
Bin YANG ; Yan YU ; Jing CHEN ; Yan ZHANG ; Ye YIN ; Nan YU ; Ge CHEN ; Shifei ZHU ; Haiyan HUANG ; Yongqun YUAN ; Jihui AI ; Xinyu WANG ; Kezhen LI
Frontiers of Medicine 2018;12(5):509-517
This study was performed to evaluate the oncological and reproductive outcomes of childbearing-age women treated with fertility-sparing surgery (FSS) for non-epithelial ovarian tumors in China. One hundred and forty eight non-epithelial ovarian tumor women treated with FSS between January 1, 2000 and August 31, 2015 from two medical centers in China were identified. Progression-free survival (PFS) was 88.5%, whereas overall survival (OS) was 93.9%. Univariate analysis suggested that delivery after treatment is related to PFS (P = 0.023), whereas histology significantly influenced OS. Cox regression analysis suggested that only histology was associated with PFS and OS (P < 0.05). Among the 129 women who completed adjuvant chemotherapy (ACT), none developed amenorrhea. Among the 44 women who desired pregnancy, 35 (79.5%) successfully had 51 gestations including 35 live births without birth defects. Non-epithelial ovarian tumors can achieve fulfilling prognosis after FSS and chemotherapy. Histology might be the only independent prognostic factor for PFS and OS. FSS followed by ACT appeared to have little or no effect on fertility. Meanwhile, postoperative pregnancy did not increase the PFS or OS. Use of gonadotropin-releasing hormone agonist was not beneficial for fertility.
Adolescent
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Adult
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Chemotherapy, Adjuvant
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adverse effects
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Child
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China
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Female
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Humans
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Infertility, Female
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etiology
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prevention & control
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Neoplasm Staging
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Organ Sparing Treatments
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Ovarian Neoplasms
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drug therapy
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surgery
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Pregnancy
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Pregnancy Rate
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Prognosis
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Retrospective Studies
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Survival Analysis
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Young Adult
10.Analysis of medical ethical review in Chinese Journal of Endemiology in 2013-2016
Chinese Journal of Endemiology 2018;37(1):77-82
Objective To understand the review situation of medical ethics in scientific research and prevention and control of endemic diseases,raise awareness of ethical review,and to promote rapid and healthy development in scientific research for control of endemic diseases.Methods The method of retrospective analysis was used,articles on original articles,field epidemiological investigations and clinical medicines published by Chinese Journal of Endemiology from 2013 to 2016 were collected.Examination of medical ethics in national,provincial and municipal fund programs and non fund projects was carried out.Statistical analysis was performed using Cochran-Armitage trend test and Cochran-Mantel-Haenszel (CMH) test.Results A total of 642 articles were collected from 2013 to 2016 and 25 articles were excluded.①The total number of papers published after medical ethics review was in a upward trend,the difference was statistically significant in trend test (Z =4.84,P <0.01);and the papers were increased from 14.8% (20/135) in 2013 to 38.2% (66/173) in 2016 and compared among different years,the differences were statistically significant (x2 =23.43,P < 0.01).The papers of original articles and field epidemiological investigations published were in a upward trend,the difference was statistically significant in trend test (Z =4.32,2.14,P < 0.01 or < 0.05);and the papers were increased from 12.3% (7/57),13.2% (9/68) in 2013 to 48.6% (36/74),27.3% (24/88) in 2016 and compared among different years,the differences were statistically significant (x2 =18.61,4.57,P < 0.01 or < 0.05).②The total number of papers published which was supported by various fund programs that had past the medical ethical review was in a upward trend,the difference was statistically significant in trend test (Z =5.27,P < 0.01);and the papers were increased from 13.3% (14/105)in 2013 to 42.4% (53/125) in 2016,compared among different years,the differences were statistically significant (x2 =27.69,P < 0.01).The total number of papers published in the national,provincial programs was in a upward trend,the difference was statistically significant in the trend test (Z =4.14,3.21,P < 0.01);and the papers were increased from 16.0% (8/50),10.0% (5/50) in 2013 to 51.7% (31/60),32.7% (17/52) in 2016,compared among different years,the differences were statistically significant (x2 =17.05,10.27,P < 0.01).③The total number of papers published and approved or marked with approval numbers by the ethics committee was in a upward trend,the difference was statistically significant in trend test (Z =5.74,5.44,P < 0.01);and the papers were increased from 0.7% (1/135),0 (0/135) in 2013 to 21.4% (37/173),11.0% (19/173) in 2016,compared among different years,the differences were statistically significant (x2 =32.90,29.55,P < 0.01).④The total number of papers published with informed consent or signed was in a upward trend,the difference was statistically significant in trend test (Z =2.56,2.14,P < 0.05);and the papers were increased from 15.6% (21/135),4.4% (6/135) in 2013 to 26.6% (46/173),11.0%(19/173) in 2016,compared among different years,the differences were statistically significant (x2 =6.54,4.60,P < 0.05).Conclusions Medical ethical review is more and more widely used in scientific research and prevention and control of endemic diseases;scientific research workers attach great importance to the ethics review of research projects.However,there are still omissions and missing reports in some projects and articles.The editorial department and editors need to guide the author to raise the author's understanding of the importance of ethical review.

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