Despite the availability of an effective vaccine, hepatitis B virus (HBV) infection remains a major health problem, with more than 350 million chronically infected people worldwide and over 1 million annual deaths due...Despite the availability of an effective vaccine, hepatitis B virus (HBV) infection remains a major health problem, with more than 350 million chronically infected people worldwide and over 1 million annual deaths due to cirrhosis and liver cancer. HBV mutations are primarily generated due both to a lack of proofreading capacity by HBV polymerase and to host immune pressure, which is a very important factor for predicting disease progression and therapeutic outcomes. Several types of HBV precore/core (preC/C) mutations have been described to date. The host immune response against T cells drives mutation in the preC/C region. Specifically, preC/C mutations in the MHC class II restricted region are more common than in other regions and are significantly related to hepatocellular carcinoma. Certain mutations, including preC G1896A, are also significantly related to HBeAg-negative chronic infection. This review article mainly focuses on the HBV preC/C mutations that are related to disease severity and on the HBeAg serostatus of chronically infected patients.展开更多
Of 350 million people worldwide are chronically infected with hepatitis B virus(HBV)and are at risk of developing cirrhosis and hepatocellular carcinoma(HCC)later in life.HBV is the most diverse DNA virus,and its geno...Of 350 million people worldwide are chronically infected with hepatitis B virus(HBV)and are at risk of developing cirrhosis and hepatocellular carcinoma(HCC)later in life.HBV is the most diverse DNA virus,and its genome is composed of four open reading frames:Presurface antigen/surface antigen gene(preS/S),precore/core gene(preC/C),polymerase gene(P),and theχgene(χ).HBV produces quasispecies naturally or in response to antiviral agents because of the absence of proofreading activity amid reverse transcription and a high replication rate.The virus has 10 genotypes(A to J)with different geographical distributions.There are various HBV mutations in the HBV genome,including preC/C mutations,preS/S mutations,P gene mutations,andχgene mutations.The core promoter region plays a vital part in the replication,morphogenesis and pathogenesis of the virus.The precore region also plays a crucial role in viral replication.Both core promoter and precore mutations rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity.preC/C mutations are associated with liver disease progression.Precore mutations stop hepatitis B e antigen(HBeAg)production and basal core promoter mutations downregulate HBeAg production.Mutations in the basal core promoter are also associated with increased HBV replication and an increased incidence of advanced liver diseases such as cirrhosis and HCC.The emergence of antiviral-resistant mutations is the main reason for treatment failure.This review focuses mainly on preC/C promoter mutations and their correlation with genotypes and liver disease severity.Thorough perception and knowledge of HBV genetic variety and mutants could be vital to discover techniques for the prognosis and control of HBV infection.展开更多
INTRODUCTION Hepatitis B is one of the common infectious diseases,which severely impairs the health of the people in our country and has close relationship
AIM:To investigate precore/basal core promoter(PC/BCP) mutants throughout hepatitis B virus(HBV) infection and to determine their relationship to hepatitis B early antigen(HBeA g) titers.METHODS:We enrolled 191 patien...AIM:To investigate precore/basal core promoter(PC/BCP) mutants throughout hepatitis B virus(HBV) infection and to determine their relationship to hepatitis B early antigen(HBeA g) titers.METHODS:We enrolled 191 patients in various stages of HBV infection at the Huashan Hospital and the Taizhou Municipal Hospital from 2010 to 2012.None of the patients received antiviral therapy.HBV DNA from serum,was quantified by real-time PCR.The HBV genotype was determined by direct sequencing of the S gene.We used the Simpleprobe ultrasensitivequantitative method to detect PC/BCP mutants in each patient.We compared the strain number,percentage,and the changes in PC/BCP mutants in different phases,and analyzed the relationship between PC/BCP mutants and HBe Ag by multiple linear regression and logistic regression.RESULTS:Patients with HBV infection(n = 191) were assigned to groups by phase:Immune tolerance(IT) = 55,Immune clearance(IC) = 67,Low-replicative(LR) = 49,and HBeA g-negative hepatitis(ENH) = 20.Of the patients(male,112; female,79) enrolled,122 were HBe Ag-positive and 69 were HBe Ag-negative.The median age was 33 years(range:18-78 years).PC and BCP mutation detection rates were 84.82%(162/191) and 96.86%(185/191),respectively.In five HBe Ag-negative cases,we detected double mutation G1896A/G1899 A.The logarithm value of PC mutant quantities(log10 PC) significantly differed in IT,IC,and LR phases,as well as in the ENH phase(F = 49.350,P < 0.001).The logarithm value of BCP mutant quantities(log10 BCP) also differed during the four phases(F = 25.530,P < 0.001).Log10 PC and log10 BCP values were high in the IT and IC phases,decreased in the LR phase,and increased in the ENH phase,although the absolute value at this point remained lower than that in the IT and IC phases.PC mutant quantity per total viral load(PC%) and BCP mutant quantity per total viral load(BCP%) differed between phases(F = 20.040,P < 0.001; F = 10.830,P < 0.001),with PC% and BCP% gradually increasing in successive phases.HBeA g titers negatively correlated with PC%(Spearman's rho =-0.354,P < 0.001) and BCP%(Spearman's rho =-0.395,P < 0.001).The negative correlation between PC% and HBeA g status was significant(B =-5.281,P = 0.001),but there was no such correlation between BCP% and HBeA g status(B =-0.523,P = 0.552).CONCLUSION:PC/BCP mutants become predominant in a dynamic and continuous process.Log10 PC,log10 BCP,PC% and BCP% might be combined to evaluate disease progression.PC% determines HBeA g status.展开更多
AIM： To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma. METH...AIM： To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma. METHODS： The mean follow-up time was 83.6 ± 39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA （HBV DNA） level and hepatitis B e antigen （HBeAg） were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development. RESULTS： During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio： 95.74 （12.13-891.31）, P 〈 0.0001], male sex [odds ratio： 7.61 （2.20-47.95）; P = 0.006], and higher Iogzo HBV DNA [odds ratio： 4.69 （1.16-20.43）; P 〈 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio： 26.51 （2.36-381.47）; P = 0.007], presence of precore mutants [odds ratio： 4.23 （1.53-19.58）, P = 0.02] and presence of basal core promoter mutants [odds ratio： 2.93 （1.24-7.57）; P = 0.02] were independent predictors for progression to hepatocellular carcinoma. CONCLUSION： Our results show that high levels of baseline serum HBV DNA are associated with non- hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.展开更多
Naturally occurred precore(PC,G1896A)and/or basal core promoter(BCP,A1762T/G1764A)mutations are prevalent in chronic HBV-infected patients,especially those under HBeAg-negative status.However,the replicative capacity ...Naturally occurred precore(PC,G1896A)and/or basal core promoter(BCP,A1762T/G1764A)mutations are prevalent in chronic HBV-infected patients,especially those under HBeAg-negative status.However,the replicative capacity of HBV with PC/BCP mutations remains ambiguous.Herein,meta-analysis showed that,only under HBeAg-negative status,the serum HBV DNA load in patients with PC mutation was 7.41-fold higher than those without the mutation.Both PC mutation alone and BCPþPC mutations promoted HBV replication in cell and hydrodynamic injection mouse models.In human hepatocyte chimeric mouse model,BCPþPC mutations led to elevated replicative capacity and intrahepatic core protein accumulation.Mechanistically,preC RNA harboring PC mutation could serve as mRNA to express core and P proteins,and such pgRNA-like function favored the maintenance of cccDNA pool under HBeAg-negative status.Additionally,BCPþPC mutations induced more extensive and severe human hepatocyte damage as well as activated endoplasmic reticulum stress and TNF signaling pathway in livers of chimeric mice.This study indicates that HBeAg-negative patients should be monitored on HBV mutations regularly and are expected to receive early antiviral treatment to prevent disease progression.展开更多
AIM： To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children. METHODS： We investigated a large pediatric popul...AIM： To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children. METHODS： We investigated a large pediatric population of 155 European children （mean age 10.9 years） with chronic hepatitis B by PCR and direct sequencing. Ninety were HBeAg positive and 65 had seroconversion to anti-HBe. Additionally genotyping was performed. RESULTS： Seventy-four （48%） of the sequenced HBV strains were attributed to genotype D and 81 （52%） to genotype A. In the group of 90 HBeAg positive patients, 2 （2.2%） 1896-G-to-A transitions leading to precore stop codon mutation were found, and in the group of 65 anti-HBe positive children, 5 （7.7%） were identified harbouring HBeAg-minus mutants. The difference was not statistically significant （P= 0.13）. CONCLUSIONS： HBeAg minus variants as predominant viral HB strains play a minor role in the course of chronic hepatitis B in European children.展开更多
Aim The 3’-base specific polymerase chain reaction (3’- BS- PCR) method was es-tablished to investigate the relationship between the mutation of precore region of Hepatitis B virus(HBV) and the liver damage to the p...Aim The 3’-base specific polymerase chain reaction (3’- BS- PCR) method was es-tablished to investigate the relationship between the mutation of precore region of Hepatitis B virus(HBV) and the liver damage to the patients caused by HBV and the possibility of HBV precore gene in-tegration in liver cells。 Mdthods According to the DNA sequence of precore region of HBV,themethod of 3’- BS- PCR is applied to analyze the point mutation site 1896 of HBV precore in 126 clini-cal serum specimens and 23 hepatoeellular carcinoma (HCC) patients’ tissues and serum whose trmorshave been surgically excised and pathologically diagnosed.Rdsults The point mutation in site 1896 ofHBV precore has been successfully rates of preore gene of HBV in the 23 patients’ tissues and serum are52.2 % (12/23) and 30.4 % (7/23) respectively.Conclusion The established method for HBV ore-core mutation analysis is simple and results can well repeated.It has provided a new approach to clinicalHBV research and its relationship to liver damage.The results obtained suggested that HBV precoremutation exists in a wide range among serum and tissue of the patients infected by HBV and HCC pa-tients,and the pre-c gene of HBV can not be detected in the serum of 21.8% of the HCC patients(tissue HBV precore gene positive).We may deduce that there may be the integration of HBV precoregenee in the genome of liver cells,which may play an important role in the carcinogenesis of HCC.展开更多
The Martian core mainly contains iron,nickel and some light elements.However,controversies remain about the structure and chemical composition of the Martian core due to a lack of samples and marsquake data.Recently,t...The Martian core mainly contains iron,nickel and some light elements.However,controversies remain about the structure and chemical composition of the Martian core due to a lack of samples and marsquake data.Recently,the InSight lander collected long-term marsquake data,which improved the Martian interior structure model.B ased on the preliminary analysis of marsquake data,Mars has a molten liquid core with a radius of around 1700 km.As the Martian core has a smaller density and lower temperature than pure iron at corresponding pressure and temperature conditions,some light elements are introduced to reduce the density and liquidus temperature.With various methods for seismic analysis,in-situ high-pressure and high-temperature experiments,and first-principal calculations,the Martian core composition and evolution models have been updated in the past few years.Here,we review those studies on the light elements in the Martian core from four aspects including(1)high-temperature and high-pressure experiments,(2)marsquake data,(3)mineral physics model with molecular dynamics simulations and(4)cosmochemistry investigation.We discussed the effect of different light elements on the Martian core s density,sound velocity and liquidus temperature.Moreover,the review examines the varieties,abundances and forms of light elements in the Martian core.展开更多
[Objectives]To investigate the clinical efficacy of core stability training combined with conventional rehabilitation in the functional recovery of patients suffering from chronic low back pain.[Methods]A randomized c...[Objectives]To investigate the clinical efficacy of core stability training combined with conventional rehabilitation in the functional recovery of patients suffering from chronic low back pain.[Methods]A randomized controlled trial design was employed in this study.Ninety patients with chronic low back pain were recruited and randomly assigned to either a control group(n=45),which received conventional rehabilitation,or an experimental group(n=45),which received conventional rehabilitation combined with core stability training.Both groups underwent treatment for 6 weeks.Assessments were conducted using the visual analogue scale(VAS),Oswestry disability index(ODI),and finger-to-floor test prior to treatment,6 weeks following treatment,and during the follow-up period,respectively.[Results]Prior to treatment,no statistically significant differences were observed between the two patient groups in terms of general information and various baseline measurements(P>0.05).Following 6 weeks of treatment and throughout the follow-up period,both groups demonstrated significant improvements in VAS scores,ODI scores,and lumbar anteflexion range of motion compared to baseline measurements(P<0.05).Notably,the magnitude of improvement in the experimental group exceeded that of the control group,with this inter-group difference reaching statistical significance(P<0.05).No serious adverse reactions were reported during the treatment process.[Conclusions]Core stability training combined with conventional rehabilitation can significantly enhance the alleviation of pain and functional impairments in patients suffering from chronic low back pain.This approach holds valuable implications for the optimization of rehabilitation treatment protocols.展开更多
We read with great interest Deng et al.’s study 1 comparing sextant(6-core)and 12-core systematic biopsy in theMRI-targeted era,which valuably challenges the“more cores=higher accuracy”dogma by proposing a precisio...We read with great interest Deng et al.’s study 1 comparing sextant(6-core)and 12-core systematic biopsy in theMRI-targeted era,which valuably challenges the“more cores=higher accuracy”dogma by proposing a precision sampling strategy based on prostate cancer’s spatial distribution,aligning with personalized diagnosis trends.展开更多
Deep tight reservoirs exhibit complex stress and seepage fields due to varying pore structures,thus the seepage characteristics are significant for enhancing oil production.This study conducted triaxial compression an...Deep tight reservoirs exhibit complex stress and seepage fields due to varying pore structures,thus the seepage characteristics are significant for enhancing oil production.This study conducted triaxial compression and permeability tests to investigate the mechanical and seepage properties of tight sandstone.A digital core of tight sandstone was built using Computed Tomography(CT)scanning,which was divided into matrix and pore phases by a pore equivalent diameter threshold.A fluid-solid coupling model was established to investigate the seepage characteristics at micro-scale.The results showed that increasing the confining pressure decreased porosity,permeability,and flow velocity,with the pore phase becoming the dominant seepage channel.Cracks and large pores closed first under increasing pressure,resulted in a steep drop in permeability.However,permeability slightly decreased under high confining pressure,which followed a first-order exponential function.Flow velocity increased with seepage pressure.And the damage mainly occurred in stress-concentration regions under low seepage pressure.Seepage behavior followed linear Darcy flow,the damage emerged at seepage entrances under high pressure,which decreased rock elastic modulus and significantly increased permeability.展开更多
The application of liquid core reduction(LCR)technology in thin slab continuous casting can refine the internal microstruc-tures of slabs and improve their production efficiency.To avoid crack risks caused by large de...The application of liquid core reduction(LCR)technology in thin slab continuous casting can refine the internal microstruc-tures of slabs and improve their production efficiency.To avoid crack risks caused by large deformation during the LCR process and to minimize the thickness of the slab in bending segments,the maximum theoretical reduction amount and the corresponding reduction scheme for the LCR process must be determined.With SPA-H weathering steel as a specific research steel grade,the distributions of tem-perature and deformation fields of a slab with the LCR process were analyzed using a three-dimensional thermal-mechanical finite ele-ment model.High-temperature tensile tests were designed to determine the critical strain of corner crack propagation and intermediate crack initiation with various strain rates and temperatures,and a prediction model of the critical strain for two typical cracks,combining the effects of strain rate and temperature,was proposed by incorporating the Zener-Hollomon parameter.The crack risks with different LCR schemes were calculated using the crack risk prediction model,and the maximum theoretical reduction amount for the SPA-H slab with a transverse section of 145 mm×1600 mm was 41.8 mm,with corresponding reduction amounts for Segment 0 to Segment 4 of 15.8,7.3,6.5,6.4,and 5.8 mm,respectively.展开更多
Research on the mechanical–electrical properties is crucial for designing and preparing high-temperature superconducting(HTS)cables.Various winding core structures can influence the mechanical–electrical behavior of...Research on the mechanical–electrical properties is crucial for designing and preparing high-temperature superconducting(HTS)cables.Various winding core structures can influence the mechanical–electrical behavior of cables,but the impact of alterations in the winding core structure on the mechanical–electrical behavior of superconducting cables remains unclear.This paper presents a 3D finite element model to predict the performance of three cables with different core structures when subjected to transverse compression and axial tension.The three cables analyzed are CORC(conductor-on-round-core),CORT(conductor-on-round-tube),and HFRC(conductor-on-spiral-tube).A parametric analysis is carried out by varying the core diameter and inner-to-outer diameter ratio.Results indicate that the CORT cable demonstrates better performance in transverse compression compared to the CORC cable,aligning with experimental data.Among the three cables,the HFRC cables exhibit the weakest resistance to transverse deformation.However,the HFRC cable demonstrates superior tensile deformation resistance compared to the CORT cable,provided that the transverse compression properties are maintained.Finite element results also show that the optimum inner-to-outer diameter ratios for achieving the best transverse compression performance are approximately 0.8 for CORT cables and 0.6 for HFRC cables.Meanwhile,the study explores the effect of structural changes in HTS cable winding cores on their electromagnetic properties.It recommends utilizing small tape gaps,lower frequencies,and spiral core construction to minimize eddy losses.The findings presented in this paper offer valuable insights for the commercialization and practical manufacturing of HTS cables.展开更多
For the first time,the linear and nonlinear vibrations of composite rectangular sandwich plates with various geometric patterns of lattice core have been analytically examined in this work.The plate comprises a lattic...For the first time,the linear and nonlinear vibrations of composite rectangular sandwich plates with various geometric patterns of lattice core have been analytically examined in this work.The plate comprises a lattice core located in the middle and several homogeneous orthotropic layers that are symmetrical relative to it.For this purpose,the partial differential equations of motion have been derived based on the first-order shear deformation theory,employing Hamilton’s principle and Von Kármán’s nonlinear displacement-strain relations.Then,the nonlinear partial differential equations of the plate are converted into a time-dependent nonlinear ordinary differential equation(Duffing equation)by applying the Galerkin method.From the solution of this equation,the natural frequencies are extracted.Then,to calculate the non-linear frequencies of the plate,the non-linear equation of the plate has been solved analytically using the method of multiple scales.Finally,the effect of some critical parameters of the system,such as the thickness,height,and different angles of the stiffeners on the linear and nonlinear frequencies,has been analyzed in detail.To confirmthe solution method,the results of this research have been compared with the reported results in the literature and finite elements in ABAQUS,and a perfect match is observed.The results reveal that the geometry and configuration of core ribs strongly affect the natural frequencies of the plate.展开更多
Coral reef limestone(CRL)constitutes a distinctive marine carbonate formation with complex mechanical properties.This study investigates the multiscale damage and fracture mechanisms of CRL through integrated experime...Coral reef limestone(CRL)constitutes a distinctive marine carbonate formation with complex mechanical properties.This study investigates the multiscale damage and fracture mechanisms of CRL through integrated experimental testing,digital core technology,and theoretical modelling.Two CRL types with contrasting mesostructures were characterized across three scales.Macroscopically,CRL-I and CRL-II exhibited mean compressive strengths of 8.46 and 5.17 MPa,respectively.Mesoscopically,CRL-I featured small-scale highly interconnected pores,whilst CRL-II developed larger stratified pores with diminished connectivity.Microscopically,both CRL matrices demonstrated remarkable similarity in mineral composition and mechanical properties.A novel voxel average-based digital core scaling methodology was developed to facilitate numerical simulation of cross-scale damage processes,revealing network-progressive failure in CRL-I versus directional-brittle failure in CRL-II.Furthermore,a damage statistical constitutive model based on digital core technology and mesoscopic homogenisation theory established quantitative relationships between microelement strength distribution and macroscopic mechanical behavior.These findings illuminate the fundamental mechanisms through which mesoscopic structure governs the macroscopic mechanical properties of CRL.展开更多
基金Supported by A National Research Foundation grant of Ministry of Science, ICT and Future Planning, South Korea, No. NRF-2015R1C1A1A02037267a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, the Ministry of Health and Welfare, South Korea, No. HI14C0955
文摘Despite the availability of an effective vaccine, hepatitis B virus (HBV) infection remains a major health problem, with more than 350 million chronically infected people worldwide and over 1 million annual deaths due to cirrhosis and liver cancer. HBV mutations are primarily generated due both to a lack of proofreading capacity by HBV polymerase and to host immune pressure, which is a very important factor for predicting disease progression and therapeutic outcomes. Several types of HBV precore/core (preC/C) mutations have been described to date. The host immune response against T cells drives mutation in the preC/C region. Specifically, preC/C mutations in the MHC class II restricted region are more common than in other regions and are significantly related to hepatocellular carcinoma. Certain mutations, including preC G1896A, are also significantly related to HBeAg-negative chronic infection. This review article mainly focuses on the HBV preC/C mutations that are related to disease severity and on the HBeAg serostatus of chronically infected patients.
文摘Of 350 million people worldwide are chronically infected with hepatitis B virus(HBV)and are at risk of developing cirrhosis and hepatocellular carcinoma(HCC)later in life.HBV is the most diverse DNA virus,and its genome is composed of four open reading frames:Presurface antigen/surface antigen gene(preS/S),precore/core gene(preC/C),polymerase gene(P),and theχgene(χ).HBV produces quasispecies naturally or in response to antiviral agents because of the absence of proofreading activity amid reverse transcription and a high replication rate.The virus has 10 genotypes(A to J)with different geographical distributions.There are various HBV mutations in the HBV genome,including preC/C mutations,preS/S mutations,P gene mutations,andχgene mutations.The core promoter region plays a vital part in the replication,morphogenesis and pathogenesis of the virus.The precore region also plays a crucial role in viral replication.Both core promoter and precore mutations rescue the virus from host immune surveillance and result in the formation of mutated strains that may have altered pathogenicity.preC/C mutations are associated with liver disease progression.Precore mutations stop hepatitis B e antigen(HBeAg)production and basal core promoter mutations downregulate HBeAg production.Mutations in the basal core promoter are also associated with increased HBV replication and an increased incidence of advanced liver diseases such as cirrhosis and HCC.The emergence of antiviral-resistant mutations is the main reason for treatment failure.This review focuses mainly on preC/C promoter mutations and their correlation with genotypes and liver disease severity.Thorough perception and knowledge of HBV genetic variety and mutants could be vital to discover techniques for the prognosis and control of HBV infection.
基金the Natural Science Foundation of Anhui Province,No.9741006Natural Science Foundation of Anhui Educational Commission,No.JL-97-077.
文摘INTRODUCTION Hepatitis B is one of the common infectious diseases,which severely impairs the health of the people in our country and has close relationship
基金Supported by National Science and Technology Major Project of China,No.2012ZX10002007-001-002 and No.2013ZX10002001(to Zhang JM)the National Natural Science Foundation of China,No.81271833 and No.81471933(to Zhang JM)+1 种基金the Science and Technology Plan Project of Taizhou,Zhejiang province,No.1402ky19(to Tu WH and Hou W)the Scientific Research Project of Taizhou University,Zhejiang province,No:2014PY054(to Tu WH and Hou W)
文摘AIM:To investigate precore/basal core promoter(PC/BCP) mutants throughout hepatitis B virus(HBV) infection and to determine their relationship to hepatitis B early antigen(HBeA g) titers.METHODS:We enrolled 191 patients in various stages of HBV infection at the Huashan Hospital and the Taizhou Municipal Hospital from 2010 to 2012.None of the patients received antiviral therapy.HBV DNA from serum,was quantified by real-time PCR.The HBV genotype was determined by direct sequencing of the S gene.We used the Simpleprobe ultrasensitivequantitative method to detect PC/BCP mutants in each patient.We compared the strain number,percentage,and the changes in PC/BCP mutants in different phases,and analyzed the relationship between PC/BCP mutants and HBe Ag by multiple linear regression and logistic regression.RESULTS:Patients with HBV infection(n = 191) were assigned to groups by phase:Immune tolerance(IT) = 55,Immune clearance(IC) = 67,Low-replicative(LR) = 49,and HBeA g-negative hepatitis(ENH) = 20.Of the patients(male,112; female,79) enrolled,122 were HBe Ag-positive and 69 were HBe Ag-negative.The median age was 33 years(range:18-78 years).PC and BCP mutation detection rates were 84.82%(162/191) and 96.86%(185/191),respectively.In five HBe Ag-negative cases,we detected double mutation G1896A/G1899 A.The logarithm value of PC mutant quantities(log10 PC) significantly differed in IT,IC,and LR phases,as well as in the ENH phase(F = 49.350,P < 0.001).The logarithm value of BCP mutant quantities(log10 BCP) also differed during the four phases(F = 25.530,P < 0.001).Log10 PC and log10 BCP values were high in the IT and IC phases,decreased in the LR phase,and increased in the ENH phase,although the absolute value at this point remained lower than that in the IT and IC phases.PC mutant quantity per total viral load(PC%) and BCP mutant quantity per total viral load(BCP%) differed between phases(F = 20.040,P < 0.001; F = 10.830,P < 0.001),with PC% and BCP% gradually increasing in successive phases.HBeA g titers negatively correlated with PC%(Spearman's rho =-0.354,P < 0.001) and BCP%(Spearman's rho =-0.395,P < 0.001).The negative correlation between PC% and HBeA g status was significant(B =-5.281,P = 0.001),but there was no such correlation between BCP% and HBeA g status(B =-0.523,P = 0.552).CONCLUSION:PC/BCP mutants become predominant in a dynamic and continuous process.Log10 PC,log10 BCP,PC% and BCP% might be combined to evaluate disease progression.PC% determines HBeA g status.
文摘AIM： To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma. METHODS： The mean follow-up time was 83.6 ± 39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA （HBV DNA） level and hepatitis B e antigen （HBeAg） were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development. RESULTS： During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio： 95.74 （12.13-891.31）, P 〈 0.0001], male sex [odds ratio： 7.61 （2.20-47.95）; P = 0.006], and higher Iogzo HBV DNA [odds ratio： 4.69 （1.16-20.43）; P 〈 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio： 26.51 （2.36-381.47）; P = 0.007], presence of precore mutants [odds ratio： 4.23 （1.53-19.58）, P = 0.02] and presence of basal core promoter mutants [odds ratio： 2.93 （1.24-7.57）; P = 0.02] were independent predictors for progression to hepatocellular carcinoma. CONCLUSION： Our results show that high levels of baseline serum HBV DNA are associated with non- hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.
基金supported by National Key R&D Program of China(2023YFC2306800)National Natural Science Foundation of China(No.82072280 and No.82272315)Beijing Municipal Natural Science Foundation(No.7212063 and No.7222108).
文摘Naturally occurred precore(PC,G1896A)and/or basal core promoter(BCP,A1762T/G1764A)mutations are prevalent in chronic HBV-infected patients,especially those under HBeAg-negative status.However,the replicative capacity of HBV with PC/BCP mutations remains ambiguous.Herein,meta-analysis showed that,only under HBeAg-negative status,the serum HBV DNA load in patients with PC mutation was 7.41-fold higher than those without the mutation.Both PC mutation alone and BCPþPC mutations promoted HBV replication in cell and hydrodynamic injection mouse models.In human hepatocyte chimeric mouse model,BCPþPC mutations led to elevated replicative capacity and intrahepatic core protein accumulation.Mechanistically,preC RNA harboring PC mutation could serve as mRNA to express core and P proteins,and such pgRNA-like function favored the maintenance of cccDNA pool under HBeAg-negative status.Additionally,BCPþPC mutations induced more extensive and severe human hepatocyte damage as well as activated endoplasmic reticulum stress and TNF signaling pathway in livers of chimeric mice.This study indicates that HBeAg-negative patients should be monitored on HBV mutations regularly and are expected to receive early antiviral treatment to prevent disease progression.
文摘AIM： To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children. METHODS： We investigated a large pediatric population of 155 European children （mean age 10.9 years） with chronic hepatitis B by PCR and direct sequencing. Ninety were HBeAg positive and 65 had seroconversion to anti-HBe. Additionally genotyping was performed. RESULTS： Seventy-four （48%） of the sequenced HBV strains were attributed to genotype D and 81 （52%） to genotype A. In the group of 90 HBeAg positive patients, 2 （2.2%） 1896-G-to-A transitions leading to precore stop codon mutation were found, and in the group of 65 anti-HBe positive children, 5 （7.7%） were identified harbouring HBeAg-minus mutants. The difference was not statistically significant （P= 0.13）. CONCLUSIONS： HBeAg minus variants as predominant viral HB strains play a minor role in the course of chronic hepatitis B in European children.
基金Project supportec by the Natural Science Foundation of Anhui Province,No 9741006 and Natural Science Foundation of Anhui Educational Commission,No.JL-97-077
文摘Aim The 3’-base specific polymerase chain reaction (3’- BS- PCR) method was es-tablished to investigate the relationship between the mutation of precore region of Hepatitis B virus(HBV) and the liver damage to the patients caused by HBV and the possibility of HBV precore gene in-tegration in liver cells。 Mdthods According to the DNA sequence of precore region of HBV,themethod of 3’- BS- PCR is applied to analyze the point mutation site 1896 of HBV precore in 126 clini-cal serum specimens and 23 hepatoeellular carcinoma (HCC) patients’ tissues and serum whose trmorshave been surgically excised and pathologically diagnosed.Rdsults The point mutation in site 1896 ofHBV precore has been successfully rates of preore gene of HBV in the 23 patients’ tissues and serum are52.2 % (12/23) and 30.4 % (7/23) respectively.Conclusion The established method for HBV ore-core mutation analysis is simple and results can well repeated.It has provided a new approach to clinicalHBV research and its relationship to liver damage.The results obtained suggested that HBV precoremutation exists in a wide range among serum and tissue of the patients infected by HBV and HCC pa-tients,and the pre-c gene of HBV can not be detected in the serum of 21.8% of the HCC patients(tissue HBV precore gene positive).We may deduce that there may be the integration of HBV precoregenee in the genome of liver cells,which may play an important role in the carcinogenesis of HCC.
基金financially supported by the National Natural Science Foundation of China(grant no.42120104005)Guizhou Provincial 2021 Science and Technology Subsidies(grant no.GZ2021SIG)+1 种基金Guizhou Provincial Science and Technology Projects(grant nos.ZK[2024]087GCC[2023]060)。
文摘The Martian core mainly contains iron,nickel and some light elements.However,controversies remain about the structure and chemical composition of the Martian core due to a lack of samples and marsquake data.Recently,the InSight lander collected long-term marsquake data,which improved the Martian interior structure model.B ased on the preliminary analysis of marsquake data,Mars has a molten liquid core with a radius of around 1700 km.As the Martian core has a smaller density and lower temperature than pure iron at corresponding pressure and temperature conditions,some light elements are introduced to reduce the density and liquidus temperature.With various methods for seismic analysis,in-situ high-pressure and high-temperature experiments,and first-principal calculations,the Martian core composition and evolution models have been updated in the past few years.Here,we review those studies on the light elements in the Martian core from four aspects including(1)high-temperature and high-pressure experiments,(2)marsquake data,(3)mineral physics model with molecular dynamics simulations and(4)cosmochemistry investigation.We discussed the effect of different light elements on the Martian core s density,sound velocity and liquidus temperature.Moreover,the review examines the varieties,abundances and forms of light elements in the Martian core.
文摘[Objectives]To investigate the clinical efficacy of core stability training combined with conventional rehabilitation in the functional recovery of patients suffering from chronic low back pain.[Methods]A randomized controlled trial design was employed in this study.Ninety patients with chronic low back pain were recruited and randomly assigned to either a control group(n=45),which received conventional rehabilitation,or an experimental group(n=45),which received conventional rehabilitation combined with core stability training.Both groups underwent treatment for 6 weeks.Assessments were conducted using the visual analogue scale(VAS),Oswestry disability index(ODI),and finger-to-floor test prior to treatment,6 weeks following treatment,and during the follow-up period,respectively.[Results]Prior to treatment,no statistically significant differences were observed between the two patient groups in terms of general information and various baseline measurements(P>0.05).Following 6 weeks of treatment and throughout the follow-up period,both groups demonstrated significant improvements in VAS scores,ODI scores,and lumbar anteflexion range of motion compared to baseline measurements(P<0.05).Notably,the magnitude of improvement in the experimental group exceeded that of the control group,with this inter-group difference reaching statistical significance(P<0.05).No serious adverse reactions were reported during the treatment process.[Conclusions]Core stability training combined with conventional rehabilitation can significantly enhance the alleviation of pain and functional impairments in patients suffering from chronic low back pain.This approach holds valuable implications for the optimization of rehabilitation treatment protocols.
文摘We read with great interest Deng et al.’s study 1 comparing sextant(6-core)and 12-core systematic biopsy in theMRI-targeted era,which valuably challenges the“more cores=higher accuracy”dogma by proposing a precision sampling strategy based on prostate cancer’s spatial distribution,aligning with personalized diagnosis trends.
基金financially supported by the National Natural Science Foundation of China(Nos.42272153 and 42472195)the Research Fund of PetroChina Tarim Oilfield Company(No.671023060003)the Research Fund of China National Petroleum Corporation Limited(No.2023ZZ16YJ04).
文摘Deep tight reservoirs exhibit complex stress and seepage fields due to varying pore structures,thus the seepage characteristics are significant for enhancing oil production.This study conducted triaxial compression and permeability tests to investigate the mechanical and seepage properties of tight sandstone.A digital core of tight sandstone was built using Computed Tomography(CT)scanning,which was divided into matrix and pore phases by a pore equivalent diameter threshold.A fluid-solid coupling model was established to investigate the seepage characteristics at micro-scale.The results showed that increasing the confining pressure decreased porosity,permeability,and flow velocity,with the pore phase becoming the dominant seepage channel.Cracks and large pores closed first under increasing pressure,resulted in a steep drop in permeability.However,permeability slightly decreased under high confining pressure,which followed a first-order exponential function.Flow velocity increased with seepage pressure.And the damage mainly occurred in stress-concentration regions under low seepage pressure.Seepage behavior followed linear Darcy flow,the damage emerged at seepage entrances under high pressure,which decreased rock elastic modulus and significantly increased permeability.
基金supported by the National Natural Science Foundation of China(No.52474355)the Liaoning Province Science and Technology Plan Joint Program(Key Research and Development Program Project),China(Nos.2022JH25/10200003 and 2023JH2/101800058).
文摘The application of liquid core reduction(LCR)technology in thin slab continuous casting can refine the internal microstruc-tures of slabs and improve their production efficiency.To avoid crack risks caused by large deformation during the LCR process and to minimize the thickness of the slab in bending segments,the maximum theoretical reduction amount and the corresponding reduction scheme for the LCR process must be determined.With SPA-H weathering steel as a specific research steel grade,the distributions of tem-perature and deformation fields of a slab with the LCR process were analyzed using a three-dimensional thermal-mechanical finite ele-ment model.High-temperature tensile tests were designed to determine the critical strain of corner crack propagation and intermediate crack initiation with various strain rates and temperatures,and a prediction model of the critical strain for two typical cracks,combining the effects of strain rate and temperature,was proposed by incorporating the Zener-Hollomon parameter.The crack risks with different LCR schemes were calculated using the crack risk prediction model,and the maximum theoretical reduction amount for the SPA-H slab with a transverse section of 145 mm×1600 mm was 41.8 mm,with corresponding reduction amounts for Segment 0 to Segment 4 of 15.8,7.3,6.5,6.4,and 5.8 mm,respectively.
基金supported by the National Natural Science Foundation of China(12072136).
文摘Research on the mechanical–electrical properties is crucial for designing and preparing high-temperature superconducting(HTS)cables.Various winding core structures can influence the mechanical–electrical behavior of cables,but the impact of alterations in the winding core structure on the mechanical–electrical behavior of superconducting cables remains unclear.This paper presents a 3D finite element model to predict the performance of three cables with different core structures when subjected to transverse compression and axial tension.The three cables analyzed are CORC(conductor-on-round-core),CORT(conductor-on-round-tube),and HFRC(conductor-on-spiral-tube).A parametric analysis is carried out by varying the core diameter and inner-to-outer diameter ratio.Results indicate that the CORT cable demonstrates better performance in transverse compression compared to the CORC cable,aligning with experimental data.Among the three cables,the HFRC cables exhibit the weakest resistance to transverse deformation.However,the HFRC cable demonstrates superior tensile deformation resistance compared to the CORT cable,provided that the transverse compression properties are maintained.Finite element results also show that the optimum inner-to-outer diameter ratios for achieving the best transverse compression performance are approximately 0.8 for CORT cables and 0.6 for HFRC cables.Meanwhile,the study explores the effect of structural changes in HTS cable winding cores on their electromagnetic properties.It recommends utilizing small tape gaps,lower frequencies,and spiral core construction to minimize eddy losses.The findings presented in this paper offer valuable insights for the commercialization and practical manufacturing of HTS cables.
文摘For the first time,the linear and nonlinear vibrations of composite rectangular sandwich plates with various geometric patterns of lattice core have been analytically examined in this work.The plate comprises a lattice core located in the middle and several homogeneous orthotropic layers that are symmetrical relative to it.For this purpose,the partial differential equations of motion have been derived based on the first-order shear deformation theory,employing Hamilton’s principle and Von Kármán’s nonlinear displacement-strain relations.Then,the nonlinear partial differential equations of the plate are converted into a time-dependent nonlinear ordinary differential equation(Duffing equation)by applying the Galerkin method.From the solution of this equation,the natural frequencies are extracted.Then,to calculate the non-linear frequencies of the plate,the non-linear equation of the plate has been solved analytically using the method of multiple scales.Finally,the effect of some critical parameters of the system,such as the thickness,height,and different angles of the stiffeners on the linear and nonlinear frequencies,has been analyzed in detail.To confirmthe solution method,the results of this research have been compared with the reported results in the literature and finite elements in ABAQUS,and a perfect match is observed.The results reveal that the geometry and configuration of core ribs strongly affect the natural frequencies of the plate.
基金National Key Research and Development Program of China (No.2021YFC3100800)the National Natural Science Foundation of China (Nos.42407235 and 42271026)+1 种基金the Project of Sanya Yazhou Bay Science and Technology City (No.SCKJ-JYRC-2023-54)supported by the Hefei advanced computing center
文摘Coral reef limestone(CRL)constitutes a distinctive marine carbonate formation with complex mechanical properties.This study investigates the multiscale damage and fracture mechanisms of CRL through integrated experimental testing,digital core technology,and theoretical modelling.Two CRL types with contrasting mesostructures were characterized across three scales.Macroscopically,CRL-I and CRL-II exhibited mean compressive strengths of 8.46 and 5.17 MPa,respectively.Mesoscopically,CRL-I featured small-scale highly interconnected pores,whilst CRL-II developed larger stratified pores with diminished connectivity.Microscopically,both CRL matrices demonstrated remarkable similarity in mineral composition and mechanical properties.A novel voxel average-based digital core scaling methodology was developed to facilitate numerical simulation of cross-scale damage processes,revealing network-progressive failure in CRL-I versus directional-brittle failure in CRL-II.Furthermore,a damage statistical constitutive model based on digital core technology and mesoscopic homogenisation theory established quantitative relationships between microelement strength distribution and macroscopic mechanical behavior.These findings illuminate the fundamental mechanisms through which mesoscopic structure governs the macroscopic mechanical properties of CRL.
