1.METTL3 Regulates the Proliferation,Migration,and Invasion of Uveal Melanoma Cell via Modifying m6A Methylation
Meilan WANG ; Tianqi ZHAO ; Qi SHI ; Lili HAO ; Lian LIU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(4):628-638
[Objectives]To investigate the effect of METTL3 on the malignant biological behaviors of uveal melanoma cells and to verify whether this effect is related to m6A methylation.[Methods]Uveal melanoma cell models with METTL3 knockdown,overexpression,and point mutations at m6A-related catalytic sites were constructed via lentivirus transfection.Transwell assays were used to assess cell migration and invasion;CCK8 assays were used to measure cell proliferation and flow cytometry was used to analyze apoptosis and cycle changes.[Results]The proliferation,migration and invasion abilities of C918 and MUM-2B cells with METTL3 knockdown were significantly decreased(P<0.001),while the apoptosis rate was increased.The proportion of cells in G1 phase significantly increased,whereas the proportion in the S phase significantly decreased.Cells overexpressing METTL3 showed significantly enhanced proliferation,migration and invasion abilities(P<0.001),along with a decreased apoptosis rate.In C918 cells,the proportion of cells in G1 phase decreased significantly,while the proportion in S phase increased significantly.The cell cycle distribution of MUM-2B cells did not change remarkably.Following point mutation of m6A-related catalytic sites,cell proliferation,migration and invasion decreased,and the apoptosis rate increased.In MUM-2B cells,the percentage of cells in G1 phase significantly increased;the percentage in S phase significantly decreased and the percentage in G2 phase slightly decreased.In C918 cells,the percentage of G1 phase cells significantly increased,with no significant changes in the proportions of S and G2 phases.[Conclusions]The proliferation,invasion and metastasis of uveal melanoma cells were positively correlated with the expression of METTL3,while the apoptosis rate was negatively correlated.Changes in METTL3 levels differentially affect the cell cycles in different cell lines.The effects of METTL3 on the proliferation,migration and invasion of uveal melanoma cells are related to m6A methylation modification.
2.METTL3 Regulates the Proliferation,Migration,and Invasion of Uveal Melanoma Cell via Modifying m6A Methylation
Meilan WANG ; Tianqi ZHAO ; Qi SHI ; Lili HAO ; Lian LIU
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(4):628-638
[Objectives]To investigate the effect of METTL3 on the malignant biological behaviors of uveal melanoma cells and to verify whether this effect is related to m6A methylation.[Methods]Uveal melanoma cell models with METTL3 knockdown,overexpression,and point mutations at m6A-related catalytic sites were constructed via lentivirus transfection.Transwell assays were used to assess cell migration and invasion;CCK8 assays were used to measure cell proliferation and flow cytometry was used to analyze apoptosis and cycle changes.[Results]The proliferation,migration and invasion abilities of C918 and MUM-2B cells with METTL3 knockdown were significantly decreased(P<0.001),while the apoptosis rate was increased.The proportion of cells in G1 phase significantly increased,whereas the proportion in the S phase significantly decreased.Cells overexpressing METTL3 showed significantly enhanced proliferation,migration and invasion abilities(P<0.001),along with a decreased apoptosis rate.In C918 cells,the proportion of cells in G1 phase decreased significantly,while the proportion in S phase increased significantly.The cell cycle distribution of MUM-2B cells did not change remarkably.Following point mutation of m6A-related catalytic sites,cell proliferation,migration and invasion decreased,and the apoptosis rate increased.In MUM-2B cells,the percentage of cells in G1 phase significantly increased;the percentage in S phase significantly decreased and the percentage in G2 phase slightly decreased.In C918 cells,the percentage of G1 phase cells significantly increased,with no significant changes in the proportions of S and G2 phases.[Conclusions]The proliferation,invasion and metastasis of uveal melanoma cells were positively correlated with the expression of METTL3,while the apoptosis rate was negatively correlated.Changes in METTL3 levels differentially affect the cell cycles in different cell lines.The effects of METTL3 on the proliferation,migration and invasion of uveal melanoma cells are related to m6A methylation modification.
3.Quantitative analysis of three-dimensional deformity indexes of the first metatarsal bone after osteotomy and orthosis for hallux valgus deformity
Xiaoliang ZHAO ; Meilan SUN ; Tianyuan YAN ; Shizhe ZHANG ; Guochang NIU ; Yulong GUAN ; Hua LI
Chinese Journal of Tissue Engineering Research 2024;33(33):5302-5307
BACKGROUND:The displacement change parameters of the bone structure of the first metatarsal bone at the two-dimensional level of hallux valgus deformity are of great significance for clinical diagnosis and treatment,while the quantitative analysis of the three-dimensional deformity index may have some influences on the postoperative efficacy. OBJECTIVE:To explore the quantitative change of the three-dimensional deformity index of the first metatarsal bone after routine osteotomy and orthosis for hallux valgus deformity and to provide reference for clinical work. METHODS:100 patients with hallux valgus deformity(foot)in Hengshui People's Hospital from October 2020 to April 2023 were selected and all of them underwent conventional osteotomy and orthosis.Foot function was assessed by the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale 6 months after surgery.Anterolateral X-rays of the foot in weight-bearing position and CT images in simulated weight-bearing position were taken before surgery and 6 months after surgery.The three-dimensional deformity indexes of the first metatarsal bone before and after surgery were quantitatively analyzed in patients with different ages,genders and therapeutic effects,including first-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle.The value of the difference of three-dimensional deformity indexes of the first metatarsal bone before and after operation in evaluating the curative effect was analyzed. RESULTS AND CONCLUSION:(1)Six months after operation,the American Orthopedic Foot and Ankle Society score was 75-98(88.25±4.14)points,among which 56 cases were excellent,28 cases were good,14 cases were average,and 2 cases were poor.The excellent and good rate was 84%(84/100).(2)Compared with the preoperative results,first-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle were significantly improved in patients of different ages and genders 6 months after surgery(P<0.05).First-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle were all lower in patients with good curative effect 6 months after surgery than those with poor curative effect,and the difference before and after surgery was greater than those with poor curative effect(P<0.05).(3)The area under the curve of the difference evaluation of the first metatarsal three-dimensional deformity index before and after surgery was above 0.7,and the area under the curve of the combined evaluation of all indexes was the largest(0.902),which was significantly greater than the first metatarsal rotation α angle and distal metatarsal articular angle(P<0.05).(4)The quantitative analysis of the three-dimensional deformity index of the first metatarsal in patients with hallux valgus deformity is related to the postoperative effect,which has important guiding significance for improving the accuracy and comprehensiveness of preoperative evaluation and improving the treatment plan.
4.Analysis on clinicopathologic features and prognosis of proliferative glomerulonephritis with monoclonal IgG deposits
Rui LU ; Ye CHEN ; Di WANG ; Lijuan ZHAO ; Meilan ZHOU ; Ming BAI ; Lijie HE ; Shiren SUN
The Journal of Practical Medicine 2024;40(24):3468-3475
Objective To analyze the clinicopathological features,treatment and prognosis of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposition.Methods The clinical data,renal pathology,treatment and prognosis of patients with PGNMID diagnosed by renal biopsy in Xijing Hospital from January 2018 to January 2024 were retrospectively analyzed and summarized.Results A total of 28 patients were enrolled in this study,with a male to female ratio of 4:3.The clinical manifestations were proteinuria(100%),hematuria(82.1%),renal insufficiency(28.6%),and low complement C3 or C4 emia(32.1%).One patient(3.6%)had serum monoclonal immunoglobulin,and 5 patients(17.9%)had abnormal serum free light chain ratio.The deposition of immunoglobulin in the kidney was IgG3 in 24 cases,IgG1 in 4 cases,and IgG3κwas the most common type(17 cases).Then there are 24 cases(85.7%)of MPGN,3 cases(10.7%)characterized by EPGN,1 case(3.6%)of MGN.Under electron microscope,most of the electron-dense deposits were found in the mesangial area and subendothelium,and a few were accompanied by subepithelial deposits.The follow-up time ranged from 3 to 56 months.Until the last follow-up,a total of 5 patients entered ESRD,of which 2 patients died,1 patient underwent peritoneal dialysis,1 patient underwent hemodialysis,and 1 patient underwent preparation for renal replacement therapy.Follow-up of 1 year,2 years,3 years renal total response rate of 32.1%,57.1%and 64.2%respectively.According to the situation of kidney ease into remission group(n=16)and non-remission group(n=12).The average age of the remission group was 44±17.35 years,including 8 males(50%);The average age of the non-remission group was 59.83±18.09 years,including 8 males(66.7%).The age,nT-proBNP,troponin I and urea nitrogen of the non-remission group were higher than those of the remission group,and the differences were statistically significant(P<0.05).Among the 5 patients with renal complete remission,2 were treated with BD(bortezomib combined with dexamethasone),1 was treated with Dara,and the remaining 2 were treated with steroids combined with immunosuppressants.Conclusions The clinical manifestations of PGNMID are proteinuria,hematuria and renal insufficiency.Under light microscope,MPGN was the main manifestation,and IgG3κwas the most common subtype.Based on bortezomib treatment can obtain good hematology and kidney remission rate.Dara may be a safe and effective drug for the treatment of PGNMID,the best treatment needs further exploration.
5.Analysis on clinicopathologic features and prognosis of proliferative glomerulonephritis with monoclonal IgG deposits
Rui LU ; Ye CHEN ; Di WANG ; Lijuan ZHAO ; Meilan ZHOU ; Ming BAI ; Lijie HE ; Shiren SUN
The Journal of Practical Medicine 2024;40(24):3468-3475
Objective To analyze the clinicopathological features,treatment and prognosis of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposition.Methods The clinical data,renal pathology,treatment and prognosis of patients with PGNMID diagnosed by renal biopsy in Xijing Hospital from January 2018 to January 2024 were retrospectively analyzed and summarized.Results A total of 28 patients were enrolled in this study,with a male to female ratio of 4:3.The clinical manifestations were proteinuria(100%),hematuria(82.1%),renal insufficiency(28.6%),and low complement C3 or C4 emia(32.1%).One patient(3.6%)had serum monoclonal immunoglobulin,and 5 patients(17.9%)had abnormal serum free light chain ratio.The deposition of immunoglobulin in the kidney was IgG3 in 24 cases,IgG1 in 4 cases,and IgG3κwas the most common type(17 cases).Then there are 24 cases(85.7%)of MPGN,3 cases(10.7%)characterized by EPGN,1 case(3.6%)of MGN.Under electron microscope,most of the electron-dense deposits were found in the mesangial area and subendothelium,and a few were accompanied by subepithelial deposits.The follow-up time ranged from 3 to 56 months.Until the last follow-up,a total of 5 patients entered ESRD,of which 2 patients died,1 patient underwent peritoneal dialysis,1 patient underwent hemodialysis,and 1 patient underwent preparation for renal replacement therapy.Follow-up of 1 year,2 years,3 years renal total response rate of 32.1%,57.1%and 64.2%respectively.According to the situation of kidney ease into remission group(n=16)and non-remission group(n=12).The average age of the remission group was 44±17.35 years,including 8 males(50%);The average age of the non-remission group was 59.83±18.09 years,including 8 males(66.7%).The age,nT-proBNP,troponin I and urea nitrogen of the non-remission group were higher than those of the remission group,and the differences were statistically significant(P<0.05).Among the 5 patients with renal complete remission,2 were treated with BD(bortezomib combined with dexamethasone),1 was treated with Dara,and the remaining 2 were treated with steroids combined with immunosuppressants.Conclusions The clinical manifestations of PGNMID are proteinuria,hematuria and renal insufficiency.Under light microscope,MPGN was the main manifestation,and IgG3κwas the most common subtype.Based on bortezomib treatment can obtain good hematology and kidney remission rate.Dara may be a safe and effective drug for the treatment of PGNMID,the best treatment needs further exploration.
6.Mixed study on the status quo and influencing factors of psychological resilience of in-service nurses in Hunan Province
Zhen LI ; Meilan QIN ; Yuelan QIN ; Bei GONG ; Ke TANG ; Zeya SHI ; Qiongling ZHAO ; Fang XIONG ; Ping YUAN ; Huan WAN
Chinese Journal of Modern Nursing 2020;26(20):2711-2717
Objective:To explore the current status and influencing factors of psychological resilience in in-service nurses in Hunan Province, and provide a certain reference for the development of nursing human resource management and occupational mental health.Methods:A mixed study method was adopted. Quantitative study: in August 2018, a total of 749 in-serve nurses from hospitals in Hunan Province were selected by convenient sampling and investigated with the general information questionnaire and Conner-Davidson Resilience Scale (CD-RISC) . SPSS 23.0 was used for statistical analysis. Qualitative study: totally 21 in-service nurses who participated in the quantitative study were randomly selected for semi-structured interviews. Based on the principle of data saturation, the subject analysis method was used to organize the data.Results:The total CD-RISC score of the 749 in-service nurses was (87.28±13.28) , higher than (65.40±13.90) of the domestic norm, and the difference was statistically significant ( P<0.01) ; the average score of each dimension in descending order was (3.69±0.55) for strength, (3.41±0.58) for toughness, and (3.34±0.60) for optimism. There were statistically significant differences between the total CD-RISC score of in-service nurses with different ages, educational levels, working years, type of affiliation, form of employment, and professional title ( F=7.295, 5.446, 6.915, 3.238, 4.342, 7.914; P<0.05) ; Multi-factor analysis showed that age and education level were the main influencing factors ( P<0.05) . Two themes were extracted from the qualitative study, namely internal factors and external factors. The internal factors included the lack of personal adaptability and mental health guidance awareness, while the external factors included differences in hospital management culture, and lack of psychological service institutions, professionals and trust. Conclusions:The psychological resilience of in-service nurses in Hunan Province is higher than that of domestic norms, and is affected by both internal and external factors. It is recommended to enhance the nurses' rights protection bill in future organization and management, attach importance to their on-the-job education and provide personalized psychological service channels for employees, and further strengthen the hospital's internal psychosocial service construction.
7.Investigation and research on the current situation of leadership of new nurses
Zhen LI ; Yuelan QIN ; Bei GONG ; Zeya SHI ; Ke TANG ; Huan WAN ; Meilan QIN ; Ping YUAN ; Qiongling ZHAO ; Fang XIONG
Chinese Journal of Modern Nursing 2019;25(1):54-57
Objective? To investigate the leadership status of new nurses, and to provide some reference for the training and education of new nurses and efficient quality nursing service. Methods? In September 2018, a total of 129 new nurses from a ClassⅢ Grade A hospital were randomly recruited by convenience sampling method. Questionnaire survey was conducted to compare the difference of leadership among new nurses with different characteristics by General Information Questionnaire and Nurse Leadership Questionnaire. A total of 129 questionnaires were sent out and 125 valid questionnaires were collected. Results? The average leadership score of the 125 new nurses was (3.59±0.67). The score of nursing professional ability dimension was the highest (3.73±0.64), and the score of critical thinking ability dimension was the lowest (3.47±0.71). The scores of five dimensions of interpersonal communication ability, communication ability, critical thinking ability, planning and organizing ability and self-care ability of new nurses of different genders in the nurse leadership questionnaire were compared, and the differences were statistically significant (t=-3.950,-3.145,-3.389,-3.451,-2.179;P<0.05). The difference in critical thinking ability score of new nurses with different marital status was statistically significant (t=3.235,P< 0.01). Conclusions? The overall level of leadership status of new nurses is low. It is suggested that in the standardized training and education of newly recruited nurses, early education and training of career leadership should be emphasized, and the strengths of different groups of nurses should be brought into play, so as to improve their professional value and quality service.
8.Tung Tree (Vernicia fordii) Genome ProvidesA Resource for Understanding Genome Evolution and Improved Oil Production
Zhang LIN ; Liu MEILAN ; Long HONGXU ; Dong WEI ; Pasha ASHER ; Esteban EDDI ; Li WENYING ; Yang XIAOMING ; Li ZE ; Song AIXIA ; Ran DUO ; Zhao GUANG ; Zeng YANLING ; Chen HAO ; Zou MING ; Li JINGJING ; Liang FAN ; Xie MEILI ; Hu JIANG ; Wang DEPENG ; Cao HEPING ; Provart J. NICHOLAS ; Zhang LIANGSHENG ; Tan XIAOFENG
Genomics, Proteomics & Bioinformatics 2019;17(6):558-575
Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73% repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.
9.Application of misoprostol combined with fentanyl and propofol in visualization of artificial abortion
Meilan LIU ; Jinyan ZHAO ; Xiaoling YU ; Weifeng LIN ; Lijun WANG
Chinese Journal of Primary Medicine and Pharmacy 2010;17(9):1165-1166
Objective To study the feasibility and security about misoprostol combined with fentanyl and propofol applied in visualization of artificial abortion.Methods 1270 cases of pregnant women who requested termination of pregnancy and voluntarily accepted abortion were selected.In the observe group,634 cases of pregnant women received oral misoprostol about 600 mg 90 minutes before surgery.After anesthetized by fentanyl and propofol,painless artificial abortion using visual abortion instrument was carried out.In the control group,636 cases of pregnant women anesthetized by fentanyl and propofol via the venous were carried out artificial abortion.The degree of cervical relaxation,loss of blood,total dose of propofol,surgical time,recovery time,the incidence of abortion complications and so on were observed.Results In the observation group and the control group,the average dosage of propofol are( 14.15 ± 2.37) ml and (16.90 ± 4.52) ml respectively;The average time required for surgery are ( 146.1 ± 38.2) s and ( 199.7 ± 37.3 ) s respectively;the average time required for awakening are ( 6.01 ± 1.90 ) min and ( 8.81 ± 2.02 )in;In the observation group,there are 405 ( 63.9% ) cases of cervical laxity markedly,in the control group,including 145 ( 22.8% ) cases of cervical laxity markedly,there is statistical significance ( P < 0.05 ) between the observation group and the control group.There are no abortion syndrome in both groups.Conclusion Misoprostol combined with fentanyl and propofol was the first choice for painless artificial abortion using ultrasound visualization.
10.A Proteomic Method For Core Needle Biopsy Sample Characterization
Jianfeng LIN ; Hongyu TIAN ; Xia GAO ; Meilan YU ; Qingxi CHEN ; Genjun XU ; Fukun ZHAO
Chinese Journal of Biochemistry and Molecular Biology 2008;24(3):221-230
Proteomic analysis of core needle biopsy (CNB) sample from patient populations is critical to our understanding of human disease,but has been hindered by its particular small size.Here,we present a method for the proteomic analysis of CNB sample based on the two dimensional electrophoresis.Proteins were extracted directly from 3 rat liver CNB specimens and a human prostate CNB sample.respectively.24 cm Immobiline DryStrip (pH 3-10NL) and 12.5% SDS-PAGE were introduced to separate the proteins.Interesting spots were analyzed by MALDI TOF/TOF mass spectrometry after tryptic digestion.With this method,consistent electrophoretic patterns of more than 2 500 protein spots were reproducibly obtained after silver staining,from rat liver CNB specimens.Qualitatively and quantitatively reproducible results also yield when the method was applied to a human prostate CNB sample.57 stochastically selected protein spots were analyzed by MALDI TOF/TOF moss spectrometry.and were identified with high confidence including faint ones.This simple and reproducible approach raises the opportunity of defining key molecular events of human disease pathologies.

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