AIM:To explore the role of a previously-found MYH9 tail domain mutation(p.E1384Q)in the pathogenesis of congenital cataract.METHODS:The cell experiments were conducted in vitro.Wild-type(WT)MYH9 and p.E1384Q mutant fr...AIM:To explore the role of a previously-found MYH9 tail domain mutation(p.E1384Q)in the pathogenesis of congenital cataract.METHODS:The cell experiments were conducted in vitro.Wild-type(WT)MYH9 and p.E1384Q mutant fragments were constructed,which was then transiently transfected into Hek293T cell lines.Western blotting and quantitative real time polymerase chain reaction(qRT-PCR)were used to analyze the protein and mRNA level of non-muscle myosin IIA(NM IIA)and F-actin in transfected cells,and fluorescence microscopy was applied to explore the subcellular localization of NM IIA and F-actin.Cell counting kit-8(CCK8),woundhealing and double staining flow cytometry assays were performed to evaluate the proliferation,migration and apoptosis function of transfected cells,respectively.Transmission electron microscope was conducted to observe the alteration of organelle structure.RESULTS:The transiently-transfected WT and p.E1384Q mutant Hek293T cell lines was constructed.Western blot demonstrated that,comparing with MYH9WT group,the relative protein amount of NM IIA and F-actin significantly decreased in MYH9E1384Q cells(P<0.001).qRT-PCR analysis revealed that the relative mRNA amount of NM IIA and F-actin also significantly reduced in MYH9E1384Q cells when compared with MYH9WT.The immunofluorescence microscopy showed that the fluorescence signal of NM IIA and F-actin significantly decreased in E1384Q cells.The diffuse cytoplasmic distribution of NM IIA in MYH9WT was changed to be clumped distribution,presenting a“speckled”pattern characterized by aggregates of small size in MYH9E1384Q.Functional study revealed that the E1384Q mutation significantly inhibited cell proliferation(P=0.003)and migration(P<0.001),and promoted apoptosis(P<0.001).Electron microscope showed that the mutation remarkably decreased the number of mitochondria(P<0.001)and changed the phenotype of mitochondria.CONCLUSION:The missense gene mutation in MYH9(p.E1384Q)causing congenital cataract results in decreased amount and altered subcellular distribution of NM IIA and F-actin,accompanied by decreased cell proliferation and migration,promotes apoptosis and mitochondrial alteration.展开更多
Diabetic retinopathy(DR)is one of the most common complications of diabetes and major cause of blindness among people over 50 years old.Current studies showed that the vascular endothelial growth factor(VEGF)played a ...Diabetic retinopathy(DR)is one of the most common complications of diabetes and major cause of blindness among people over 50 years old.Current studies showed that the vascular endothelial growth factor(VEGF)played a central role in the pathogenesis of DR,and application of anti-VEGF has been widely acknowledged in treatment of DR targeting retinal neovascularization.However,anti-VEGF therapy has several limitations such as drug resistance.It is essential to develop new drugs for future clinical practice.The vitreous takes up 80%of the whole globe volume and is in direct contact with the retina,making it possible to explore the pathogenesis of DR by studying related factors in the vitreous.This article reviewed recent studies on DR-related factors in the vitreous,elaborating the VEGF upstream hypoxia-inducible factor(HIF)pathway and downstream pathways phosphatidylinositol diphosphate(PIP2),phosphoinositide-3-kinase(PI3 K),and mitogenactivated protein kinase(MAPK)pathways.Moreover,factors other than VEGF contributing to the pathogenesis of DR in the vitreous were also summarized,which included factors in four major systems,kallikrein-kinin system such as bradykinin,plasma kallikrein,and coagulation factor XII,oxidative stress system such as lipid peroxide,and superoxide dismutase,inflammation-related factors such as interleukin-1β/6/13/37,and interferon-γ,matrix metalloproteinase(MMP)system such as MMP-9/14.Additionally,we also introduced other DR-related factorssuch as adiponectin,certain specific amino acids,noncoding RNA and renin(pro)receptor in separate studies.展开更多
AIM:To explore the efficacy of the orthokeratology lens for anisometropic myopia progression.METHODS:A retrospective study was performed.Cycloplegic refraction and axial length(AL)were collected from 50 children(10.52...AIM:To explore the efficacy of the orthokeratology lens for anisometropic myopia progression.METHODS:A retrospective study was performed.Cycloplegic refraction and axial length(AL)were collected from 50 children(10.52±1.72 y)who visited Peking University Third Hospital from July 2015 to August 2020.These children’s one eyes(Group A)received monocular orthokeratology lenses at first,after different durations(12.20±6.94 mo),their contralateral eyes(Group B)developed myopia and receive orthokeratology as well.The data in 1-year of binocular period were recorded.AL growth rate(difference of follow-up and baseline per month)were compared between two groups by paired t test.Interocular differences of AL were compared by Wilcoxon test.RESULTS:During monocular period,the AL growth rate of the Group A(0.008±0.022 mm/mo)was significantly slower than that of the Group B(0.038±0.018 mm/mo;P<0.0001).However,during binocular period,the AL growth rate of the Group A(0.026±0.014 mm/mo)was significantly faster than that of the Group B(0.016±0.015 mm/mo;P<0.0001).The AL difference between both eyes was 0.6(0.46)mm,then significantly decreased to 0.22(0.39)mm when started binocular treatment(P<0.0001).However,it was significantly increased to 0.30(0.32)mm after a year(P<0.0001),but still significantly lower than baseline(P<0.0001).CONCLUSION:The orthokeratology lens is efficient for control the AL elongation of monocular myopia eyes and reduce anisometropia.For the condition that the contralateral eyes develop myopia and receive orthokeratology lens later,there is no efficiency observed on control interocular difference of AL during binocular treatment.展开更多
BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal...BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.展开更多
Reported values （0.2 MPa-7.0 GPa） of the interlayer shear strength （ISS） of graphite are very dispersed. The main challenge to obtain a reliable value of the ISS using conventional measuring methods was the unavai...Reported values （0.2 MPa-7.0 GPa） of the interlayer shear strength （ISS） of graphite are very dispersed. The main challenge to obtain a reliable value of the ISS using conventional measuring methods was the unavailability of sufficiently large single crystalline graphite. Here we present a novel experimental method to measure the ISS, and obtain the value as -0.14 GPa. Our result can serve as an important basis for understanding mechanical behavior of graphite or graphene-based materials.展开更多
基金Supported by Beijing Municipal Natural Science Foundation(No.7202229No.7242168)China Primary Health Care Foundation(No.MTP2022C025).
文摘AIM:To explore the role of a previously-found MYH9 tail domain mutation(p.E1384Q)in the pathogenesis of congenital cataract.METHODS:The cell experiments were conducted in vitro.Wild-type(WT)MYH9 and p.E1384Q mutant fragments were constructed,which was then transiently transfected into Hek293T cell lines.Western blotting and quantitative real time polymerase chain reaction(qRT-PCR)were used to analyze the protein and mRNA level of non-muscle myosin IIA(NM IIA)and F-actin in transfected cells,and fluorescence microscopy was applied to explore the subcellular localization of NM IIA and F-actin.Cell counting kit-8(CCK8),woundhealing and double staining flow cytometry assays were performed to evaluate the proliferation,migration and apoptosis function of transfected cells,respectively.Transmission electron microscope was conducted to observe the alteration of organelle structure.RESULTS:The transiently-transfected WT and p.E1384Q mutant Hek293T cell lines was constructed.Western blot demonstrated that,comparing with MYH9WT group,the relative protein amount of NM IIA and F-actin significantly decreased in MYH9E1384Q cells(P<0.001).qRT-PCR analysis revealed that the relative mRNA amount of NM IIA and F-actin also significantly reduced in MYH9E1384Q cells when compared with MYH9WT.The immunofluorescence microscopy showed that the fluorescence signal of NM IIA and F-actin significantly decreased in E1384Q cells.The diffuse cytoplasmic distribution of NM IIA in MYH9WT was changed to be clumped distribution,presenting a“speckled”pattern characterized by aggregates of small size in MYH9E1384Q.Functional study revealed that the E1384Q mutation significantly inhibited cell proliferation(P=0.003)and migration(P<0.001),and promoted apoptosis(P<0.001).Electron microscope showed that the mutation remarkably decreased the number of mitochondria(P<0.001)and changed the phenotype of mitochondria.CONCLUSION:The missense gene mutation in MYH9(p.E1384Q)causing congenital cataract results in decreased amount and altered subcellular distribution of NM IIA and F-actin,accompanied by decreased cell proliferation and migration,promotes apoptosis and mitochondrial alteration.
基金Supported by the National Science and Technology Major Project(No.2018ZX10101004)Beijing Natural Science Foundation(No.7202229)。
文摘Diabetic retinopathy(DR)is one of the most common complications of diabetes and major cause of blindness among people over 50 years old.Current studies showed that the vascular endothelial growth factor(VEGF)played a central role in the pathogenesis of DR,and application of anti-VEGF has been widely acknowledged in treatment of DR targeting retinal neovascularization.However,anti-VEGF therapy has several limitations such as drug resistance.It is essential to develop new drugs for future clinical practice.The vitreous takes up 80%of the whole globe volume and is in direct contact with the retina,making it possible to explore the pathogenesis of DR by studying related factors in the vitreous.This article reviewed recent studies on DR-related factors in the vitreous,elaborating the VEGF upstream hypoxia-inducible factor(HIF)pathway and downstream pathways phosphatidylinositol diphosphate(PIP2),phosphoinositide-3-kinase(PI3 K),and mitogenactivated protein kinase(MAPK)pathways.Moreover,factors other than VEGF contributing to the pathogenesis of DR in the vitreous were also summarized,which included factors in four major systems,kallikrein-kinin system such as bradykinin,plasma kallikrein,and coagulation factor XII,oxidative stress system such as lipid peroxide,and superoxide dismutase,inflammation-related factors such as interleukin-1β/6/13/37,and interferon-γ,matrix metalloproteinase(MMP)system such as MMP-9/14.Additionally,we also introduced other DR-related factorssuch as adiponectin,certain specific amino acids,noncoding RNA and renin(pro)receptor in separate studies.
基金Supported by China International Medical Foundation(No.Z-2018-40)Beijing Municipal Science and Technology Commission(No.Z151100004015073)。
文摘AIM:To explore the efficacy of the orthokeratology lens for anisometropic myopia progression.METHODS:A retrospective study was performed.Cycloplegic refraction and axial length(AL)were collected from 50 children(10.52±1.72 y)who visited Peking University Third Hospital from July 2015 to August 2020.These children’s one eyes(Group A)received monocular orthokeratology lenses at first,after different durations(12.20±6.94 mo),their contralateral eyes(Group B)developed myopia and receive orthokeratology as well.The data in 1-year of binocular period were recorded.AL growth rate(difference of follow-up and baseline per month)were compared between two groups by paired t test.Interocular differences of AL were compared by Wilcoxon test.RESULTS:During monocular period,the AL growth rate of the Group A(0.008±0.022 mm/mo)was significantly slower than that of the Group B(0.038±0.018 mm/mo;P<0.0001).However,during binocular period,the AL growth rate of the Group A(0.026±0.014 mm/mo)was significantly faster than that of the Group B(0.016±0.015 mm/mo;P<0.0001).The AL difference between both eyes was 0.6(0.46)mm,then significantly decreased to 0.22(0.39)mm when started binocular treatment(P<0.0001).However,it was significantly increased to 0.30(0.32)mm after a year(P<0.0001),but still significantly lower than baseline(P<0.0001).CONCLUSION:The orthokeratology lens is efficient for control the AL elongation of monocular myopia eyes and reduce anisometropia.For the condition that the contralateral eyes develop myopia and receive orthokeratology lens later,there is no efficiency observed on control interocular difference of AL during binocular treatment.
基金Supported by the National Key Clinical Discipline,Fuzhou “14th Five-Year Plan” Clinical Key Specialty (laboratory medicine)the National Science Foundation of China,No. 82002587
文摘BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.
基金supported by the National Natural Science Foundation of China(10832005)the National Basic Research Program of China (2007CB936803)
文摘Reported values （0.2 MPa-7.0 GPa） of the interlayer shear strength （ISS） of graphite are very dispersed. The main challenge to obtain a reliable value of the ISS using conventional measuring methods was the unavailability of sufficiently large single crystalline graphite. Here we present a novel experimental method to measure the ISS, and obtain the value as -0.14 GPa. Our result can serve as an important basis for understanding mechanical behavior of graphite or graphene-based materials.
