Doubled haploid(DH)technology is an important tool in crop breeding because it can significantly accelerate the breeding process.ZmPLA1/MATL/NLD and ZmDMP are two key genes controlling haploid induction(HI)in maize,ex...Doubled haploid(DH)technology is an important tool in crop breeding because it can significantly accelerate the breeding process.ZmPLA1/MATL/NLD and ZmDMP are two key genes controlling haploid induction(HI)in maize,exhibiting a synergistic effect.However,it is unknown whether knock out of ZmDMP orthologs can stimulate HI in rice.In this study,a ZmPLA1 ortholog(OsPLA1)and two ZmDMP orthologs(OsDMP3 and OsDMP6)were identified in rice.All three genes encode plasma membrane-localized proteins and were highly expressed in mature anthers.Knockout of OsPLA1 in both Minghui 63 and Nipponbare resulted in reduced seed setting rate(SSR)and caused HI.The osdmp3,osdmp6 and the double mutant failed to trigger HI independently,nor increased the haploid induction rate(HIR)when combined with ospla1.Repeated pollinations operations of QX654A with the ospla1 mutant significantly improve SSR,while reducing HIR.RNA-seq profiling of mature ospla1 mutant anthers indicated that a large number of differentially expressed genes(DEGs)were enriched in redox homeostasis and lipid metabolic GO terms,plant hormone signal transduction,and MAPK signaling pathways.These findings provide important insights towards construction of an efficient DH breeding technology and study of the molecular mechanism of HI in rice.展开更多
Background:Multiple mitochondrial dysfunction syndromes(MMDS)are rare mitochondrial diseases caused by mutation of mitochondrial iron–sulfur cluster synthesis proteins.This study established a rat model simulating MM...Background:Multiple mitochondrial dysfunction syndromes(MMDS)are rare mitochondrial diseases caused by mutation of mitochondrial iron–sulfur cluster synthesis proteins.This study established a rat model simulating MMDS5 disease in the nervous system to investigate its pathological features and neuronal death.Methods:We generated neuron-specific Isca1 knockout rat(Isca1 flox/flox-NeuN-Cre)using CRISPR-Cas9 technology.The brain structure changes of CKO rats were studied with MRI,and the behavior abnormalities were analyzed through gait analysis and open field tests,Y maze tests and food maze tests.The pathological changes of neurons were analyzed through H&E staining,Nissl staining,and Golgi staining.Mitochondrial damage was assessed by TEM,western blot and ATP assay,and the morphology of neurons was assessed by WGA immunofluorescence to detect the death of neurons.Results:This study established the disease model of MMDS5 in the nervous system for the first time,and found that after Isca1 loss,the rats suffered from developmental retardation,epilepsy,memory impairment,massive neuronal death,reduced number of Nissl bodies and dendritic spines,mitochondrial fragmentation,cristae fracture,reduced content of respiratory chain complex protein,and reduced production of ATP.Isca1 knockout caused neuronal oncosis.Conclusions:This rat model can be used to study the pathogenesis of MMDS.In addition,compared with human MMDS5,the rat model can survive up to 8 weeks of age,effectively extending the window of clinical treatment research,and can be used for the treatment of neurological symptoms in other mitochondrial diseases.展开更多
Background:Inflammation is a complex physiological and pathological process.Although many types of inflammation are well characterized,their physiological func-tions are largely unknown.tRNA aspartic acid methyltransf...Background:Inflammation is a complex physiological and pathological process.Although many types of inflammation are well characterized,their physiological func-tions are largely unknown.tRNA aspartic acid methyltransferase 1(TRDMT1)has been implicated as a stress-related protein,but its intrinsic biological role is unclear.Methods:We constructed a Trdmt1 knockout rat and adopted the LPS-induced sepsis model.Survival curve,histopathological examination,expression of inflammatory fac-tors,and protein level of TLR4 pathway were analyzed.Results:Trdmt1 deletion had no obvious impact on development and growth.Trdmt1 de-letion slightly increased the mortality during aging.Our data showed that Trdmt1 strongly responded in LPS-treated rats,and Trdmt1 knockout rats were vulnerable to LPS treat-ment with declined survival rate.We also observed more aggravated tissue damage and more cumulative functional cell degeneration in LPS-treated knockout rats compared with control rats.Further studies showed upregulated TNF-αlevel in liver,spleen,lung,and serum tissues,which may be explained by enhanced p65 and p38 phosphorylation.Conclusions:Our data demonstrated that Trdmt1 plays a protective role in inflamma-tion by regulating the TLR4-NF-κB/MAPK-TNF-αpathway.This work provides useful information to understand the TRDMT1 function in inflammation.展开更多
Background:Natural astaxanthin(ASTA)has strong antioxidant properties and has been widely used as a health product to improve human health.However,the effects of ASTA on the reproductive performance of aging roosters ...Background:Natural astaxanthin(ASTA)has strong antioxidant properties and has been widely used as a health product to improve human health.However,the effects of ASTA on the reproductive performance of aging roosters have been poorly studied.We aimed to investigate the effects of dietary ASTA on semen quality and antioxidant capacity in aging roosters and to explore the potential mechanism of semen quality change via antioxidation defense system.Methods:In the present study,9653-week-old Jinghong No.1 layer breeder roosters were fed a corn-soybean meal basal diet containing 0,25,50,or 100 mg/kg ASTA for 6 weeks.Results:Semen quality in the ASTA groups remarkably improved than that in the control group,and antioxidant activities,the abilities to scavenge hydroxyl radicals and superoxide anions,increased gradually with ASTA addition(P<0.05).In addition,the mRNA levels of antioxidant enzymes as well as the mRNA and protein levels of the mitogen-activated protein kinase(MAPK)and nuclear factor-erythroid 2-related factor 2(Nrf2)were markedly increased in the 50-100 mg/kg ASTA group(P<0.05).Conclusions:Collectively,these results demonstrate that dietary ASTA may improve semen quality by increasing antioxidant enzyme activities and the ability to scavenge hydroxyl radicals,which may be related to upregulation of the MAPK/Nrf2 pathway.展开更多
Background:Cardiovascular diseases(CVDs)and diabetes mellitus(DM)are top two chronic comorbidities that increase the severity and mortality of COVID-19.However,how SARS-CoV-2 alters the progression of chronic diseases...Background:Cardiovascular diseases(CVDs)and diabetes mellitus(DM)are top two chronic comorbidities that increase the severity and mortality of COVID-19.However,how SARS-CoV-2 alters the progression of chronic diseases remain unclear.Methods:We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice.SARS-CoV-2’s impacts on pathogenesis of chronic diseases were studied through histopathological,virologic and molecular biology analysis.Results:Pre-existing CVDs resulted in viral invasion,ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection.Viral infection increased fasting blood glucose and reduced insulin response in DM model.Bone mineral density decreased shortly after infection,which associated with impaired PI3K/AKT/mTOR signaling.Conclusion:We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases.Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection,which further aggravated the pre-existing diseases.This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.展开更多
Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the speci...Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the specific clinical symptoms and pathogenesis remain unclear.More urgently,there is a lack of an animal model to aid research.Therefore,we selected a reported MMDS causal gene,Isca1,and established an animal model of MMDS complicated with cardiac dysplasia.Methods:The myocardium-specific Isca1 knockout heterozygote(Isca1 HET)rat was obtained by crossing the Isca1 conditional knockout(Isca1 cKO)rat with theαmyosin heavy chain Cre(α-MHC-Cre)rat.Cardiac development characteristics were determined by ECG,blood pressure measurement,echocardiography and histopatho-logical analysis.The responsiveness to pathological stimuli were observed through adriamycin treatment.Mitochondria and metabolism disorder were determined by activity analysis of mitochondrial respiratory chain complex and ATP production in myocardium.Results:ISCA1 expression in myocardium exhibited a semizygous effect.Isca1 HET rats exhibited dilated cardiomyopathy characteristics,including thin-walled ventri-cles,larger chambers,cardiac dysfunction and myocardium fibrosis.Downregulated ISCA1 led to deteriorating cardiac pathological processes at the global and organiza-tional levels.Meanwhile,HET rats exhibited typical MMDS characteristics,including damaged mitochondrial morphology and enzyme activity for mitochondrial respira-tory chain complexesⅠ,ⅡandⅣ,and impaired ATP production.Conclusion:We have established a rat model of MMDS complicated with cardiomyopathy,it can also be used as model of myocardial energy metabolism dysfunction and mitochondrial cardiomyopathy.This model can be applied to the study of the mechanism of energy metabolism in cardiovascular diseases,as well as research and development of drugs.展开更多
In order to achieve the selective hydrogenation of biodiesel at room temperature and under normal pressure,we researched the upgrading of soybean biodiesel using a dielectric-barrier discharge(DBD)reaction system.Usin...In order to achieve the selective hydrogenation of biodiesel at room temperature and under normal pressure,we researched the upgrading of soybean biodiesel using a dielectric-barrier discharge(DBD)reaction system.Using Raney-Ni as the hydrogenation catalyst,the effects of the operating parameters on the hydrogenation depth and the selectivity of biodiesel were systematically analyzed.The results show that the polyunsaturated components in soybean methyl ester were reduced by 57.04%,and that the polyunsaturated components were hydrogenated to monounsaturated components with a selectivity of 77.75%.Based on the gas chromatography and mass spectrometry(GC-MS)test results,we established a kinetic model for biodiesel hydrogenation.A comparison of the calculated and experimental results shows that the hydrogenation of the biodiesel can be described by a quasi first-order reaction model.The calculated reaction rate constants indicate that under DBD plasma reaction conditions,the hydrogenation of biodiesel has high selectivity for the formation of monounsaturated components.展开更多
Dear Editor,Doubled haploid(DH)technology can significantly accelerate the development of homozygous lines.DH breeding has achieved great success inmaize because of the discovery of the first haploid inducer,Stock6,an...Dear Editor,Doubled haploid(DH)technology can significantly accelerate the development of homozygous lines.DH breeding has achieved great success inmaize because of the discovery of the first haploid inducer,Stock6,and the development of a series of high-efficiency haploid inducers(Hu et al.,2016).Pioneering studies on the genetic basis of haploid induction(HI)revealed that loss-offunction mutation of the phospholipase gene ZmPLA1/MATL/NLD triggers HI and that the HI rate(HIR)can be dramatically enhanced by a single nucleotide substitution from T to C in ZmDMP(Jacquier et al.,2020).Remarkably,knockout of ZmPLA1/MATL/NLD homologs in rice,wheat,and foxtail millet results in HIRs of 2%–6%,5%–15%,and 2%–3%,respectively(Jacquier et al.,2020;Cheng et al.,2021).In addition,loss of function of ZmDMP-like genes enables HI in species including Arabidopsis,tomato,rapeseed,tobacco,etc.,with an average HIR of around 2%(Zhong et al.,2020,2022a,2022b).These successes have laid solid foundations for the construction of a universal DH breeding system in different crop species.More importantly,HI-Edit/IMGE systems that enable gene editing in elite germplasms have been established on the basis of HI,making HI even more important(Kelliher et al.,2019;Wang et al.,2019).展开更多
Dear Editor,Bread wheat(Triticum aestivum)is one of the most important food crops and provides approximately 20%of the food calories for human consumption.A 70%increase in wheat production is needed by 2050 to keep pa...Dear Editor,Bread wheat(Triticum aestivum)is one of the most important food crops and provides approximately 20%of the food calories for human consumption.A 70%increase in wheat production is needed by 2050 to keep pace with the growing global population(International Wheat Genome Sequencing,2014).Developing superior cultivars is an efficient way to improve yield.Nevertheless,conventional breeding is time consuming,as more than eight generations are needed to develop new plant varieties.Using doubled haploid(DH)technology,homozygous lines can be produced in only two generations,dramatically accelerating the breeding process.In wheat,haploids can be obtained by cross pollination with corn pollen followed by embryo rescue(Laurie and Bennett,1988).In maize,haploids can be induced by haploid inducer lines derived from Stock6(Liu et al.,2022).The cloning of two genes that control haploid induction(HI)in maize,MATL/ZmPLA1/NLD and ZmDMP,paved the way for DH breeding in more crop species(Jacquier et al.,2020).Further studies have shown that loss of function of TaPLAs triggers wheat HI with an efficiency of 5.88%to 31.6%(Liu et al.,2020a,2020b);this would be a promising approach for establishing a new,simple,and more efficient DH breeding method in wheat.展开更多
Aims:Minimal hepatic encephalopathy(MHE)significantly affects the prognosis of patients with cirrhosis.This study was performed to determine whether there is a difference in the prevalence of MHE among patients with c...Aims:Minimal hepatic encephalopathy(MHE)significantly affects the prognosis of patients with cirrhosis.This study was performed to determine whether there is a difference in the prevalence of MHE among patients with cirrhosis of different etiologies and whether the etiology directly influences the occurrence of MHE.Methods:This multicenter,cross-sectional study enrolled 1879 patients with confirmed cirrhosis at 40 hospitals from October 25,2021,to January 10,2023(Trial registration:https://clinicaltrials.gov/[NCT05140837]).The patients'demographics,etiologies of cirrhosis,and laboratory test results were collected.The psychometric hepatic encephalopathy score(PHES)was determined in all patients to screen for MHE.Multivariate logistic analyses were performed to identify the risk factors for MHE.Results:In total,736 patients with cirrhosis were analyzed.The prevalence of MHE was 42.0%(n=309).The primary etiology among all patients was hepatitis B virus(HBV)-related cirrhosis(71.9%[529/736]).The prevalence of MHE was significantly higher in patients with alcoholic cirrhosis(57.1%[40/70])than in those with HBV-related cirrhosis(40.6%[215/529],p=0.009)or hepatitis C virus(HCV)-related cirrhosis(38.2%[26/68],p=0.026).Age(odds ratio[OR],1.042;95%confidence interval[CI],1.024-1.059;p<0.001),duration of education(OR,0.935;95%CI,0.899-0.971;p=0.001),etiology(OR,1.740;95%CI,1.028-2.945;p=0.039),and high MELD-Na scores(OR,1.038;95%CI,1.009-1.067;p=0.009)were independent risk factors for MHE.When patients with cirrhosis of different etiologies were analyzed separately,the results showed that age(OR,1.035;95%CI,1.014-1.057;p=0.001)and duration of education(OR,0.924;95%CI,0.883-0.966;p=0.001)were risk factors for MHE among patients with HBV-related cirrhosis,whereas age(OR,1.138;95%CI,1.033-1.254;p=0.009)and creatinine concentration(OR,16.487;95%CI,1.113-244.160;p=0.042)were risk factors for MHE in patients with HCV-related cirrhosis.No risk factors for MHE were found in patients with autoimmune cirrhosis.For patients with alcoholic cirrhosis,the platelet count(OR,1.014;95%CI,1.000-1.027;p=0.045)was a risk factor for MHE.The PHES subtest results were inconsistent among patients who had MHE with cirrhosis of different etiologies.Patients with HBV-related cirrhosis performed better on Number Connection Test B and the serial dotting test than those with alcoholic cirrhosis(p=0.007 and p<0.001),better on Number Connection Test B than those with HCV-related cirrhosis(p=0.020),and better on the line tracing test than those with autoimmune cirrhosis(p=0.037).Conclusion:The etiology of cirrhosis affected the prevalence of MHE and risk factors for MHE.The domains of major cognitive impairment varied among patients with cirrhosis of different etiologies.Further studies are required to verify these findings.展开更多
To the Editor,The number of patients with liver disease exceeds 400 million in China.1 All types of hepatitis can progress to cirrhosis,and the severity of portal hypertension is a crucial factor affecting patients...To the Editor,The number of patients with liver disease exceeds 400 million in China.1 All types of hepatitis can progress to cirrhosis,and the severity of portal hypertension is a crucial factor affecting patients'clinical prognosis.2 In 2022,Chinese scientific researchers have made progress in the field of cirrhosis and portal hypertension.Accordingly,the“Top 10 Original Research in Cirrhosis and Portal Hypertension from China in 2022”project was initiated by the Chinese Portal Hypertension Alliance(CHESS).展开更多
Aim:Patients with chronic liver disease(CLD),especially cirrhosis,are at a high risk of severe illness or death from coronavirus disease-2019(COVID-19)and may have a suboptimal immune response to the severe acute resp...Aim:Patients with chronic liver disease(CLD),especially cirrhosis,are at a high risk of severe illness or death from coronavirus disease-2019(COVID-19)and may have a suboptimal immune response to the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine.This study aimed to evaluate the safety and immunogenicity of the COVID-19 booster vaccination in patients with CLD.Methods:The study protocol was prospectively registered at ClinicalTrials.gov(No.NCT05204602)after approval by the Ethics Committee.Adult participants with CLD were enrolled in this multicenter prospective study.They completed two doses of the inactivated COVID-19 vaccine and received booster doses at least 6 months later.Adverse reactions were recorded within 14 days after the booster dose.Serum samples of the enrolled patients were collected before and after booster vaccination and tested for SARS-CoV-2 receptor-binding domain(RBD)immunoglobulin G and neutralizing anti-bodies.The chi-squared or Fisher's exact test was used to compare categorical data,and the Mann-Whitney U test was used to compare continuous variables.Two-sided p<0.05 were considered statistically significant.Results:In total,63 patients were enrolled from four hospitals in China,including 29 patients with cirrhosis.The median age of all patients was 55 years,and 61.9%(39/63)were male.The vaccines were well tolerated;most adverse reactions were mild and transient,and injection site pain(6.4%;4/63)and fatigue(3.2%,2/63)were the most frequent local and systemic adverse events.Following the booster vaccination,our results showed that in the whole cohort,the levels and positive rates of anti-RBD IgG and neutralizing antibodies were significantly higher than baseline levels(all p<0.05).Conclusions:The inactivated COVID-19 booster vaccine was safe and significantly increased antibody levels and positivity rates following standard vaccination regimens in patients with CLD,especially those with cirrhosis.展开更多
Aims:Patients with liver disease may exhibit higher infection rates and mortality rates from coronavirus disease 2019(COVID-19)than healthy individuals,and vaccination against severe acute respiratory syndrome coronav...Aims:Patients with liver disease may exhibit higher infection rates and mortality rates from coronavirus disease 2019(COVID-19)than healthy individuals,and vaccination against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is an effective prevention strategy.This metaanalysis aimed to assess the effectiveness and safety of SARS-CoV-2 vaccines in patients with chronic liver disease(CLD)and post-liver transplantation(LT).Methods:The PubMed,Embase,and Cochrane databases were searched.A random-effects model meta-analysis was used to determine the seropositivity rates of SARS-CoV-2 antibodies,odds ratio(OR)compared with healthy controls(HC),risk ratio(RR)between the booster and standard vaccination regimen,and the rate of adverse reactions(ADR).Results:In the standard vaccination regimen analysis,17 controlled articles were included for effectiveness analysis,and six articles for ADR analysis.The pooled seropositivity rates of SARS-CoV-2 antibodies in patients with CLD and post-LT were 93.3%(95%confidence interval[CI]:89.0%-97.6%)and 69.1%(95%CI:63.0%-75.3%),respectively.Both rates were lower than those in HC(p<0.001).The differences remained significant after sorting by detection interval,vaccine type,antibody type,or CLD type.LT recipients showed much lower seropositivity rates of antibodies than patients with CLD(69.1%vs.93.3%)or HC(OR:0.055).The pooled total ADR rate of patients was 24.0%(95%CI:16.2%-31.8%).In the booster vaccination regimen analysis,11 prospective studies were enrolled,and the seropositivity rates of antibodies after the booster dose were increased by 27%compared with those of the standard vaccination regimen(RR:1.27,95%CI:1.15-1.41,p<0.001).Conclusion:Patients with CLD and post-LT can gain protection against COVID-19 from standard vaccines,demonstrating a potentially weaker immunogenic response than HC.Booster vaccines can compensate for this deficiency.Therefore,patients with CLD and post-LT should be prioritized for receiving the COVID-19 booster vaccine.展开更多
Aim:The transjugular intrahepatic portosystemic shunt(TIPS)procedure has been performed in China for 30 years,but our understanding of the status and difficulties associated with the use of TIPS for portal hypertensio...Aim:The transjugular intrahepatic portosystemic shunt(TIPS)procedure has been performed in China for 30 years,but our understanding of the status and difficulties associated with the use of TIPS for portal hypertension is incomplete.This study aims to investigate the current situation of the use of TIPS for portal hypertension,which should aid the development of TIPS in China.Methods:This study involved a questionnaire survey,initiated by the China Portal Hypertension Alliance(CHESS)to investigate the use of TIPS for portal hypertension in China.Questionnaires were released on the Internet between August 16,2022 and September 16,2022.Detailed information was collected from 545 hospitals contracted by the CHESS in China,which performed TIPS surgery in 2021.Results:The 545 hospitals covers the majority of hospitals in China that conduct TIPS intervention.In the survey,a total of 13,527 TIPS interventions were carried out with 94.1%(498/545)of them had a system of routine follow‐up after TIPS.The majority(42.6%[232/545])believed that the main indication of TIPS was the control of acute bleeding.Overall,48.1%(262/545)carried out early or pre‐emptive TIPS,53.0%(289/545)carried out TIPS for cavernous transformation of the portal vein,and 81.0%(441/545)chose routine embolization of collateral circulation during operation.Most used coils(97.0%[475/490])and biological glue(72.0%[353/490])as embolic materials,and 78.5%(428/545)routinely performed intraoperative portal pressure gradient measurements.When selecting TIPS stents,57.1%(311/545)chose viator‐specific stents,and 57.2%(312/545)chose conventional anticoagulation after TIPS.Conventional anticoagulation after TIPS is over a time interval of 3–6 months(55.4%[173/312]).The limitation of TIPS surgery is mainly its cost(72.3%[394/545])and insufficient understanding of the procedure by doctors in other related departments(77.4%[422/545]).Most of the hospital teams accept the use of domestic instruments in TIPS surgery(92.7%[505/545]).Conclusions:This survey shows that TIPS is an essential part of the treatment of portal hypertension in China.TIPS is widely used in Chinese patients with portal hypertension,and this survey presents a more comprehensive picture of the options and difficulties encountered in the implementation of TIPS.In the future,it is necessary to promote TIPS technology and further standardize surgical indications,routine operations,and instrument application.展开更多
Doubled haploid(DH) technology is used to obtain homozygous lines in a single generation, a technique that significantly accelerates the crop breeding trajectory. Traditionally, in vitro culture is used to generate DH...Doubled haploid(DH) technology is used to obtain homozygous lines in a single generation, a technique that significantly accelerates the crop breeding trajectory. Traditionally, in vitro culture is used to generate DHs, but this technique is limited by species and genotype recalcitrance. In vivo haploid induction(HI) through seed is widely and efficiently used in maize and was recently extended to several other crops. Here we show that in vivo HI can be triggered by mutation of DMP maternal haploid inducer genes in allopolyploid(allotetraploid) Brassica napus and Nicotiana tabacum. We developed a pipeline for selection of DMP orthologs for clustered regularly interspaced palindromic repeats mutagenesis and demonstrated average amphihaploid induction rates of2.4% and 1.2% in multiple B. napus and N. tabacum genotypes, respectively. These results further confirmed the HI ability of DMP gene in polyploid dicot crops. The DMP-HI system offers a novel DH technology to facilitate breeding in these crops. The success of this approach and the conservation of DMP genes in dicots suggest the broad applicability of this technique in other dicot crops.展开更多
Background and Aims:This study aimed to determine the performance of the non-invasive score using noncontrastenhanced MRI(CHESS-DIS score)for detecting portal hy-pertension in cirrhosis.Methods:In this international m...Background and Aims:This study aimed to determine the performance of the non-invasive score using noncontrastenhanced MRI(CHESS-DIS score)for detecting portal hy-pertension in cirrhosis.Methods:In this international multicenter,diagnostic study(ClinicalTrials.gov,NCT03766880),patients with cirrhosis who had hepatic venous pressure gradient(HVPG)measurement and noncontrast-enhanced MRI were prospectively recruited from four university hospitals in China(n=4)and Turkey(n=1)between December 2018 and April 2019.A cohort of patients was retrospectively recruited from a university hospital in Italy between March 2015 and November 2017.After segmentation of the liver on fat-suppressed T1-weighted MRI maps,CHESS-DIS score was calculated automatically by an in-house developed code based on the quantification of liver surface nodularity.Results:A total of 149 patients were included,of which 124 were from four Chinese hospitals(training cohort)and 25 were from two international hospitals(validation cohort).A positive correlation between CHESS-DIS score and HVPG was found with the correlation coefficients of 0.36(p<0.0001)and 0.55(p<0.01)for the training and validation cohorts,respectively.The area under the receiver operating characteristic curve of CHESS-DIS score in detection of clinically significant portal hypertension(CSPH)was 0.81 and 0.9 in the training and validation cohorts,respectively.The intra-class correlation coefficients for assessing the inter-and intra-observer agreement were 0.846 and 0.841,respectively.Conclusions:A non-invasive score using noncontrast-enhanced MRI was developed and proved to be significantly correlated with invasive HVPG.Besides,this score could be used to detect CSPH in patients with cirrhosis.展开更多
Corrosion performance of carbon steel in CO_2 aqueous environment containing silty sand with different sizes was investigated by immersion tests and electrochemical measurements.Silty sand could form an adsorption lay...Corrosion performance of carbon steel in CO_2 aqueous environment containing silty sand with different sizes was investigated by immersion tests and electrochemical measurements.Silty sand could form an adsorption layer on steel surface in initial period,and the sand adsorption layer was turned into a mixture film of silty sand with corrosion product in last period.The adsorption layer in 325 mesh condition(large size)had the fewest pores for H_2CO_3 transport,exhibiting the highest cathodic current inhibition.In spite of little corrosion product,the sand adsorption film formed in 325 mesh condition induced the lowest corrosion rate.For 1000 and 5000 mesh silty sand,the sand adsorption layer had some pores for H_2CO_3 transport,leading to low cathodic current inhibition and much matrix dissolution.But the adsorption layer for5000 mesh silty sand(small size)had the largest special surface area to accelerate heterogeneous precipitation of corrosion product FeCO_3.Therefore,the mixture film in 5000 mesh condition was more compact,exhibiting stronger anodic inhibition and lower corrosion rate than those in 1000 mesh condition.展开更多
Aim:To determine the tolerance and acceptance of hepatic venous pressure gradient(HVPG)measurements in patients with liver cirrhosis.Methods:This prospective international multicenter study included 271 patients with ...Aim:To determine the tolerance and acceptance of hepatic venous pressure gradient(HVPG)measurements in patients with liver cirrhosis.Methods:This prospective international multicenter study included 271 patients with cirrhosis who were scheduled to undergo HVPG measurement between October 2019 and June 2020.Data related to the tolerance and acceptance of HVPG measurements were collected using descriptive questionnaires.Results:HVPG measurements were technically successful in all 271 patients,with 141(52.0%)undergoing HVPG measurement alone.The complication rate was 0.4%.Postoperative pain was significantly lower than preoperative expected pain(p<0.001)and intraoperative pain(p<0.001),and intraoperative pain was also significantly lower than preoperative expected pain(p=0.036).No,mild,moderate,severe,and intolerable discomfort scores were reported by 36.9%,44.6%,11.1%,6.3%,and 0.4%of these patients,respectively,during HVPG measurement and by 54.6%32.5%,11.4%,1.5%,and 0%,respectively,after HVPG measurement.Of these patients,39.5%had little understanding and 10%had no understanding of the value of HVPG measurement,with 35.1%and 4.1%regarding HVPG measurements as being of little or no help,respectively.Most patients reported that they would definitely(15.5%),probably(46.9%),or possibly(29.9%)choose to undergo additional HVPG measurements again,and 62.7%regarded the cost of the procedure as acceptable.Conclusion:HVPG measurement was safe and well‐tolerated in patients with cirrhosis,but patient education and communication are warranted to improve the acceptance of this procedure.展开更多
Tissue engineering(TE)is promising for the regeneration of failed organs.However,immune rejection,shortage of seed cells,and unintegrated blood vessels restrict the development and clinical application of TE.The last ...Tissue engineering(TE)is promising for the regeneration of failed organs.However,immune rejection,shortage of seed cells,and unintegrated blood vessels restrict the development and clinical application of TE.The last factor is the most challenging and intractable.Harnessing the mature blood vessel network in existing dispensable organs could be a powerful approach to effectively overcome the obstacles.After being remodeled to harbor an immunosuppressive and proregenerative niche,these potential target organs can be transformed into other organs with specific physiological functions,compensating the latter's failed native functions.Organ transformation,such as a hepatized spleen,represents an effective and encouraging TE strategy.In this review,we discuss the current development and obstacles of TE and its feasibility and superiority in organ transformation.展开更多
Nonalcoholic fatty liver disease(NAFLD)has become the most common chronic liver disease worldwide.NAFLD‐related cirrhosis is often complicated by portal hypertension(PHT).Recent evidence showed that portal venous pr...Nonalcoholic fatty liver disease(NAFLD)has become the most common chronic liver disease worldwide.NAFLD‐related cirrhosis is often complicated by portal hypertension(PHT).Recent evidence showed that portal venous pressure(PVP)starts to rise in the early stages of NAFLD,even in absence of advanced fibrosis or cirrhosis.However,the precise pathological mechanisms of this process are still poorly understood.Lipid accumulation,hepatocellular ballooning,sinusoidal endothelial cell dysfunction,capillarization,microthrombosis,increased angiogenesis,and pericellular fibrosis may all be involved in the early development of increased PVP in NAFLD.Direct measurement of PHT is invasive and impractical in noncirrhotic NAFLD individuals and may also underestimate its severity.Thus,the development and validation of noninvasive and more accurate measurements,including new serum biomarkers,scoring models,and imaging techniques(such as ultrasonography,elastography,and magnetic resonance imaging),are urgently needed.Owing to the increasing morbidity,challenges in the prevention and management of PHT in NAFLD are unprecedented.This review article aims to briefly discuss these challenges and summarizes the mechanisms,diagnosis,and emerging therapies for PHT in people with NAFLD.展开更多
基金This work was supported by the National Key Research and Development Program of China(2022YFD1200800)the China Agriculture Research System(CARS-02-05)+1 种基金Beijing Nova Program(2023067)Yunnan Province Science and Technology Department(202305AF150026).
文摘Doubled haploid(DH)technology is an important tool in crop breeding because it can significantly accelerate the breeding process.ZmPLA1/MATL/NLD and ZmDMP are two key genes controlling haploid induction(HI)in maize,exhibiting a synergistic effect.However,it is unknown whether knock out of ZmDMP orthologs can stimulate HI in rice.In this study,a ZmPLA1 ortholog(OsPLA1)and two ZmDMP orthologs(OsDMP3 and OsDMP6)were identified in rice.All three genes encode plasma membrane-localized proteins and were highly expressed in mature anthers.Knockout of OsPLA1 in both Minghui 63 and Nipponbare resulted in reduced seed setting rate(SSR)and caused HI.The osdmp3,osdmp6 and the double mutant failed to trigger HI independently,nor increased the haploid induction rate(HIR)when combined with ospla1.Repeated pollinations operations of QX654A with the ospla1 mutant significantly improve SSR,while reducing HIR.RNA-seq profiling of mature ospla1 mutant anthers indicated that a large number of differentially expressed genes(DEGs)were enriched in redox homeostasis and lipid metabolic GO terms,plant hormone signal transduction,and MAPK signaling pathways.These findings provide important insights towards construction of an efficient DH breeding technology and study of the molecular mechanism of HI in rice.
基金CAMS Innovation Fund for Medical Sciences CIFMSGrant/Award Number:2021-I2M-1-034+3 种基金National Key Research and Development Program of ChinaGrant/Award Number:2022YFF0710702National Natural Science Foundation of ChinaGrant/Award Number:31970508。
文摘Background:Multiple mitochondrial dysfunction syndromes(MMDS)are rare mitochondrial diseases caused by mutation of mitochondrial iron–sulfur cluster synthesis proteins.This study established a rat model simulating MMDS5 disease in the nervous system to investigate its pathological features and neuronal death.Methods:We generated neuron-specific Isca1 knockout rat(Isca1 flox/flox-NeuN-Cre)using CRISPR-Cas9 technology.The brain structure changes of CKO rats were studied with MRI,and the behavior abnormalities were analyzed through gait analysis and open field tests,Y maze tests and food maze tests.The pathological changes of neurons were analyzed through H&E staining,Nissl staining,and Golgi staining.Mitochondrial damage was assessed by TEM,western blot and ATP assay,and the morphology of neurons was assessed by WGA immunofluorescence to detect the death of neurons.Results:This study established the disease model of MMDS5 in the nervous system for the first time,and found that after Isca1 loss,the rats suffered from developmental retardation,epilepsy,memory impairment,massive neuronal death,reduced number of Nissl bodies and dendritic spines,mitochondrial fragmentation,cristae fracture,reduced content of respiratory chain complex protein,and reduced production of ATP.Isca1 knockout caused neuronal oncosis.Conclusions:This rat model can be used to study the pathogenesis of MMDS.In addition,compared with human MMDS5,the rat model can survive up to 8 weeks of age,effectively extending the window of clinical treatment research,and can be used for the treatment of neurological symptoms in other mitochondrial diseases.
基金CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I 2M-1-024 and 2021-I 2M-1-034)and Beijing Municipal Natural Science Foundation(M21004)+1 种基金National Natural Science Foundation of China(31970508)111 Project of the Ministry of Education(B20095)。
文摘Background:Inflammation is a complex physiological and pathological process.Although many types of inflammation are well characterized,their physiological func-tions are largely unknown.tRNA aspartic acid methyltransferase 1(TRDMT1)has been implicated as a stress-related protein,but its intrinsic biological role is unclear.Methods:We constructed a Trdmt1 knockout rat and adopted the LPS-induced sepsis model.Survival curve,histopathological examination,expression of inflammatory fac-tors,and protein level of TLR4 pathway were analyzed.Results:Trdmt1 deletion had no obvious impact on development and growth.Trdmt1 de-letion slightly increased the mortality during aging.Our data showed that Trdmt1 strongly responded in LPS-treated rats,and Trdmt1 knockout rats were vulnerable to LPS treat-ment with declined survival rate.We also observed more aggravated tissue damage and more cumulative functional cell degeneration in LPS-treated knockout rats compared with control rats.Further studies showed upregulated TNF-αlevel in liver,spleen,lung,and serum tissues,which may be explained by enhanced p65 and p38 phosphorylation.Conclusions:Our data demonstrated that Trdmt1 plays a protective role in inflamma-tion by regulating the TLR4-NF-κB/MAPK-TNF-αpathway.This work provides useful information to understand the TRDMT1 function in inflammation.
基金This study was supported by Modern Agricultural Industry Technology System-Peking Poultry Innovation Team(BAIC04–2021)the National Key R&D Program of China(2016YFD0700201).
文摘Background:Natural astaxanthin(ASTA)has strong antioxidant properties and has been widely used as a health product to improve human health.However,the effects of ASTA on the reproductive performance of aging roosters have been poorly studied.We aimed to investigate the effects of dietary ASTA on semen quality and antioxidant capacity in aging roosters and to explore the potential mechanism of semen quality change via antioxidation defense system.Methods:In the present study,9653-week-old Jinghong No.1 layer breeder roosters were fed a corn-soybean meal basal diet containing 0,25,50,or 100 mg/kg ASTA for 6 weeks.Results:Semen quality in the ASTA groups remarkably improved than that in the control group,and antioxidant activities,the abilities to scavenge hydroxyl radicals and superoxide anions,increased gradually with ASTA addition(P<0.05).In addition,the mRNA levels of antioxidant enzymes as well as the mRNA and protein levels of the mitogen-activated protein kinase(MAPK)and nuclear factor-erythroid 2-related factor 2(Nrf2)were markedly increased in the 50-100 mg/kg ASTA group(P<0.05).Conclusions:Collectively,these results demonstrate that dietary ASTA may improve semen quality by increasing antioxidant enzyme activities and the ability to scavenge hydroxyl radicals,which may be related to upregulation of the MAPK/Nrf2 pathway.
基金National Natural Science Foundation of China,Grant/Award Number:82041008 and 32070543National Mega Projects of China for Major Infectious Diseases,Grant/Award Number:2017ZX10304402+1 种基金CAMS Initiative for Innovative Medicine of China,Grant/Award Number:2016-12M-2-006 and 2017-12M-3-015Beijing Municipal Natural Science Foundation,Grant/Award Number:M21004。
文摘Background:Cardiovascular diseases(CVDs)and diabetes mellitus(DM)are top two chronic comorbidities that increase the severity and mortality of COVID-19.However,how SARS-CoV-2 alters the progression of chronic diseases remain unclear.Methods:We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice.SARS-CoV-2’s impacts on pathogenesis of chronic diseases were studied through histopathological,virologic and molecular biology analysis.Results:Pre-existing CVDs resulted in viral invasion,ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection.Viral infection increased fasting blood glucose and reduced insulin response in DM model.Bone mineral density decreased shortly after infection,which associated with impaired PI3K/AKT/mTOR signaling.Conclusion:We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases.Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection,which further aggravated the pre-existing diseases.This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection.
基金The present work was supported in part by the Beijing Natural Science Foundation(5212017)CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-1-015)National Natural Science Foundation(31872314 and 31970508).
文摘Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the specific clinical symptoms and pathogenesis remain unclear.More urgently,there is a lack of an animal model to aid research.Therefore,we selected a reported MMDS causal gene,Isca1,and established an animal model of MMDS complicated with cardiac dysplasia.Methods:The myocardium-specific Isca1 knockout heterozygote(Isca1 HET)rat was obtained by crossing the Isca1 conditional knockout(Isca1 cKO)rat with theαmyosin heavy chain Cre(α-MHC-Cre)rat.Cardiac development characteristics were determined by ECG,blood pressure measurement,echocardiography and histopatho-logical analysis.The responsiveness to pathological stimuli were observed through adriamycin treatment.Mitochondria and metabolism disorder were determined by activity analysis of mitochondrial respiratory chain complex and ATP production in myocardium.Results:ISCA1 expression in myocardium exhibited a semizygous effect.Isca1 HET rats exhibited dilated cardiomyopathy characteristics,including thin-walled ventri-cles,larger chambers,cardiac dysfunction and myocardium fibrosis.Downregulated ISCA1 led to deteriorating cardiac pathological processes at the global and organiza-tional levels.Meanwhile,HET rats exhibited typical MMDS characteristics,including damaged mitochondrial morphology and enzyme activity for mitochondrial respira-tory chain complexesⅠ,ⅡandⅣ,and impaired ATP production.Conclusion:We have established a rat model of MMDS complicated with cardiomyopathy,it can also be used as model of myocardial energy metabolism dysfunction and mitochondrial cardiomyopathy.This model can be applied to the study of the mechanism of energy metabolism in cardiovascular diseases,as well as research and development of drugs.
基金supported by National Natural Science Foundation of China(No.51761145011)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the Jiangsu University Senior Talent Fund Project(No.12811020026)。
文摘In order to achieve the selective hydrogenation of biodiesel at room temperature and under normal pressure,we researched the upgrading of soybean biodiesel using a dielectric-barrier discharge(DBD)reaction system.Using Raney-Ni as the hydrogenation catalyst,the effects of the operating parameters on the hydrogenation depth and the selectivity of biodiesel were systematically analyzed.The results show that the polyunsaturated components in soybean methyl ester were reduced by 57.04%,and that the polyunsaturated components were hydrogenated to monounsaturated components with a selectivity of 77.75%.Based on the gas chromatography and mass spectrometry(GC-MS)test results,we established a kinetic model for biodiesel hydrogenation.A comparison of the calculated and experimental results shows that the hydrogenation of the biodiesel can be described by a quasi first-order reaction model.The calculated reaction rate constants indicate that under DBD plasma reaction conditions,the hydrogenation of biodiesel has high selectivity for the formation of monounsaturated components.
基金supported by the Hainan Yazhou Bay Seed Laboratory(project of wheat haploid induction B21HJ0501)the National Natural Science Foundation of China(32001554)+2 种基金the China Agricultural Research System(CARS-02)the Chinese Universities Scientific Fund(no.2022TC141)the China Postdoctoral Science Foundation(2022TQ0368).
文摘Dear Editor,Doubled haploid(DH)technology can significantly accelerate the development of homozygous lines.DH breeding has achieved great success inmaize because of the discovery of the first haploid inducer,Stock6,and the development of a series of high-efficiency haploid inducers(Hu et al.,2016).Pioneering studies on the genetic basis of haploid induction(HI)revealed that loss-offunction mutation of the phospholipase gene ZmPLA1/MATL/NLD triggers HI and that the HI rate(HIR)can be dramatically enhanced by a single nucleotide substitution from T to C in ZmDMP(Jacquier et al.,2020).Remarkably,knockout of ZmPLA1/MATL/NLD homologs in rice,wheat,and foxtail millet results in HIRs of 2%–6%,5%–15%,and 2%–3%,respectively(Jacquier et al.,2020;Cheng et al.,2021).In addition,loss of function of ZmDMP-like genes enables HI in species including Arabidopsis,tomato,rapeseed,tobacco,etc.,with an average HIR of around 2%(Zhong et al.,2020,2022a,2022b).These successes have laid solid foundations for the construction of a universal DH breeding system in different crop species.More importantly,HI-Edit/IMGE systems that enable gene editing in elite germplasms have been established on the basis of HI,making HI even more important(Kelliher et al.,2019;Wang et al.,2019).
基金supported by the Hainan Yazhou Bay Seed Laboratory(B21HJ0501)China Postdoctoral Science Foundation(2022TQ0368)+1 种基金China Agricultural Research System(CARS-02)Chinese Universities Scientific Fund(no.2022TC141).
文摘Dear Editor,Bread wheat(Triticum aestivum)is one of the most important food crops and provides approximately 20%of the food calories for human consumption.A 70%increase in wheat production is needed by 2050 to keep pace with the growing global population(International Wheat Genome Sequencing,2014).Developing superior cultivars is an efficient way to improve yield.Nevertheless,conventional breeding is time consuming,as more than eight generations are needed to develop new plant varieties.Using doubled haploid(DH)technology,homozygous lines can be produced in only two generations,dramatically accelerating the breeding process.In wheat,haploids can be obtained by cross pollination with corn pollen followed by embryo rescue(Laurie and Bennett,1988).In maize,haploids can be induced by haploid inducer lines derived from Stock6(Liu et al.,2022).The cloning of two genes that control haploid induction(HI)in maize,MATL/ZmPLA1/NLD and ZmDMP,paved the way for DH breeding in more crop species(Jacquier et al.,2020).Further studies have shown that loss of function of TaPLAs triggers wheat HI with an efficiency of 5.88%to 31.6%(Liu et al.,2020a,2020b);this would be a promising approach for establishing a new,simple,and more efficient DH breeding method in wheat.
基金The Innovation Groups of the National Natural Science Foundation of China,Grant/Award Number:81721002Capital Clinical Diagnosis and Treatment Technology Research and Transformation Application Project,Grant/Award Number:Z201100005520046+1 种基金Tianjin Key Medical Specialty Construction Project,Grant/Award Number:TJYXZDXK-034ATianjin Health Science and Technology Project,Grant/Award Number:TJWJ2022XK029。
文摘Aims:Minimal hepatic encephalopathy(MHE)significantly affects the prognosis of patients with cirrhosis.This study was performed to determine whether there is a difference in the prevalence of MHE among patients with cirrhosis of different etiologies and whether the etiology directly influences the occurrence of MHE.Methods:This multicenter,cross-sectional study enrolled 1879 patients with confirmed cirrhosis at 40 hospitals from October 25,2021,to January 10,2023(Trial registration:https://clinicaltrials.gov/[NCT05140837]).The patients'demographics,etiologies of cirrhosis,and laboratory test results were collected.The psychometric hepatic encephalopathy score(PHES)was determined in all patients to screen for MHE.Multivariate logistic analyses were performed to identify the risk factors for MHE.Results:In total,736 patients with cirrhosis were analyzed.The prevalence of MHE was 42.0%(n=309).The primary etiology among all patients was hepatitis B virus(HBV)-related cirrhosis(71.9%[529/736]).The prevalence of MHE was significantly higher in patients with alcoholic cirrhosis(57.1%[40/70])than in those with HBV-related cirrhosis(40.6%[215/529],p=0.009)or hepatitis C virus(HCV)-related cirrhosis(38.2%[26/68],p=0.026).Age(odds ratio[OR],1.042;95%confidence interval[CI],1.024-1.059;p<0.001),duration of education(OR,0.935;95%CI,0.899-0.971;p=0.001),etiology(OR,1.740;95%CI,1.028-2.945;p=0.039),and high MELD-Na scores(OR,1.038;95%CI,1.009-1.067;p=0.009)were independent risk factors for MHE.When patients with cirrhosis of different etiologies were analyzed separately,the results showed that age(OR,1.035;95%CI,1.014-1.057;p=0.001)and duration of education(OR,0.924;95%CI,0.883-0.966;p=0.001)were risk factors for MHE among patients with HBV-related cirrhosis,whereas age(OR,1.138;95%CI,1.033-1.254;p=0.009)and creatinine concentration(OR,16.487;95%CI,1.113-244.160;p=0.042)were risk factors for MHE in patients with HCV-related cirrhosis.No risk factors for MHE were found in patients with autoimmune cirrhosis.For patients with alcoholic cirrhosis,the platelet count(OR,1.014;95%CI,1.000-1.027;p=0.045)was a risk factor for MHE.The PHES subtest results were inconsistent among patients who had MHE with cirrhosis of different etiologies.Patients with HBV-related cirrhosis performed better on Number Connection Test B and the serial dotting test than those with alcoholic cirrhosis(p=0.007 and p<0.001),better on Number Connection Test B than those with HCV-related cirrhosis(p=0.020),and better on the line tracing test than those with autoimmune cirrhosis(p=0.037).Conclusion:The etiology of cirrhosis affected the prevalence of MHE and risk factors for MHE.The domains of major cognitive impairment varied among patients with cirrhosis of different etiologies.Further studies are required to verify these findings.
文摘To the Editor,The number of patients with liver disease exceeds 400 million in China.1 All types of hepatitis can progress to cirrhosis,and the severity of portal hypertension is a crucial factor affecting patients'clinical prognosis.2 In 2022,Chinese scientific researchers have made progress in the field of cirrhosis and portal hypertension.Accordingly,the“Top 10 Original Research in Cirrhosis and Portal Hypertension from China in 2022”project was initiated by the Chinese Portal Hypertension Alliance(CHESS).
基金prospectively registered at ClinicalTrials.gov (NCT05204602)after approval by the ethics committee (The Third Central Hospital of Tianjin,No.IRB2021-026-01Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,No.KY2021133+1 种基金Jincheng People's Hospital,No.20210603Lishui People's Hospital,No.2021[007-01]).
文摘Aim:Patients with chronic liver disease(CLD),especially cirrhosis,are at a high risk of severe illness or death from coronavirus disease-2019(COVID-19)and may have a suboptimal immune response to the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)vaccine.This study aimed to evaluate the safety and immunogenicity of the COVID-19 booster vaccination in patients with CLD.Methods:The study protocol was prospectively registered at ClinicalTrials.gov(No.NCT05204602)after approval by the Ethics Committee.Adult participants with CLD were enrolled in this multicenter prospective study.They completed two doses of the inactivated COVID-19 vaccine and received booster doses at least 6 months later.Adverse reactions were recorded within 14 days after the booster dose.Serum samples of the enrolled patients were collected before and after booster vaccination and tested for SARS-CoV-2 receptor-binding domain(RBD)immunoglobulin G and neutralizing anti-bodies.The chi-squared or Fisher's exact test was used to compare categorical data,and the Mann-Whitney U test was used to compare continuous variables.Two-sided p<0.05 were considered statistically significant.Results:In total,63 patients were enrolled from four hospitals in China,including 29 patients with cirrhosis.The median age of all patients was 55 years,and 61.9%(39/63)were male.The vaccines were well tolerated;most adverse reactions were mild and transient,and injection site pain(6.4%;4/63)and fatigue(3.2%,2/63)were the most frequent local and systemic adverse events.Following the booster vaccination,our results showed that in the whole cohort,the levels and positive rates of anti-RBD IgG and neutralizing antibodies were significantly higher than baseline levels(all p<0.05).Conclusions:The inactivated COVID-19 booster vaccine was safe and significantly increased antibody levels and positivity rates following standard vaccination regimens in patients with CLD,especially those with cirrhosis.
基金The National Key R&D Program of China,Grant/Award Number:2020YFC0860900The Emergency Key Program of Guangzhou Laboratory,Grant/Award Number:EKPG21-30-4。
文摘Aims:Patients with liver disease may exhibit higher infection rates and mortality rates from coronavirus disease 2019(COVID-19)than healthy individuals,and vaccination against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is an effective prevention strategy.This metaanalysis aimed to assess the effectiveness and safety of SARS-CoV-2 vaccines in patients with chronic liver disease(CLD)and post-liver transplantation(LT).Methods:The PubMed,Embase,and Cochrane databases were searched.A random-effects model meta-analysis was used to determine the seropositivity rates of SARS-CoV-2 antibodies,odds ratio(OR)compared with healthy controls(HC),risk ratio(RR)between the booster and standard vaccination regimen,and the rate of adverse reactions(ADR).Results:In the standard vaccination regimen analysis,17 controlled articles were included for effectiveness analysis,and six articles for ADR analysis.The pooled seropositivity rates of SARS-CoV-2 antibodies in patients with CLD and post-LT were 93.3%(95%confidence interval[CI]:89.0%-97.6%)and 69.1%(95%CI:63.0%-75.3%),respectively.Both rates were lower than those in HC(p<0.001).The differences remained significant after sorting by detection interval,vaccine type,antibody type,or CLD type.LT recipients showed much lower seropositivity rates of antibodies than patients with CLD(69.1%vs.93.3%)or HC(OR:0.055).The pooled total ADR rate of patients was 24.0%(95%CI:16.2%-31.8%).In the booster vaccination regimen analysis,11 prospective studies were enrolled,and the seropositivity rates of antibodies after the booster dose were increased by 27%compared with those of the standard vaccination regimen(RR:1.27,95%CI:1.15-1.41,p<0.001).Conclusion:Patients with CLD and post-LT can gain protection against COVID-19 from standard vaccines,demonstrating a potentially weaker immunogenic response than HC.Booster vaccines can compensate for this deficiency.Therefore,patients with CLD and post-LT should be prioritized for receiving the COVID-19 booster vaccine.
文摘Aim:The transjugular intrahepatic portosystemic shunt(TIPS)procedure has been performed in China for 30 years,but our understanding of the status and difficulties associated with the use of TIPS for portal hypertension is incomplete.This study aims to investigate the current situation of the use of TIPS for portal hypertension,which should aid the development of TIPS in China.Methods:This study involved a questionnaire survey,initiated by the China Portal Hypertension Alliance(CHESS)to investigate the use of TIPS for portal hypertension in China.Questionnaires were released on the Internet between August 16,2022 and September 16,2022.Detailed information was collected from 545 hospitals contracted by the CHESS in China,which performed TIPS surgery in 2021.Results:The 545 hospitals covers the majority of hospitals in China that conduct TIPS intervention.In the survey,a total of 13,527 TIPS interventions were carried out with 94.1%(498/545)of them had a system of routine follow‐up after TIPS.The majority(42.6%[232/545])believed that the main indication of TIPS was the control of acute bleeding.Overall,48.1%(262/545)carried out early or pre‐emptive TIPS,53.0%(289/545)carried out TIPS for cavernous transformation of the portal vein,and 81.0%(441/545)chose routine embolization of collateral circulation during operation.Most used coils(97.0%[475/490])and biological glue(72.0%[353/490])as embolic materials,and 78.5%(428/545)routinely performed intraoperative portal pressure gradient measurements.When selecting TIPS stents,57.1%(311/545)chose viator‐specific stents,and 57.2%(312/545)chose conventional anticoagulation after TIPS.Conventional anticoagulation after TIPS is over a time interval of 3–6 months(55.4%[173/312]).The limitation of TIPS surgery is mainly its cost(72.3%[394/545])and insufficient understanding of the procedure by doctors in other related departments(77.4%[422/545]).Most of the hospital teams accept the use of domestic instruments in TIPS surgery(92.7%[505/545]).Conclusions:This survey shows that TIPS is an essential part of the treatment of portal hypertension in China.TIPS is widely used in Chinese patients with portal hypertension,and this survey presents a more comprehensive picture of the options and difficulties encountered in the implementation of TIPS.In the future,it is necessary to promote TIPS technology and further standardize surgical indications,routine operations,and instrument application.
基金supported by National Key Research and Development Program of China (2016YFD0101200, 2018YFD0100201)China Agriculture Research System of MOF and MARA, National Natural Science Foundation of China (91935303, 32001554)+1 种基金the 2020 Research Program of Sanya Yazhou Bay Science and Technology City (SKJC-2020-02-003)China Postdoctoral Science Foundation (2020TQ0356)
文摘Doubled haploid(DH) technology is used to obtain homozygous lines in a single generation, a technique that significantly accelerates the crop breeding trajectory. Traditionally, in vitro culture is used to generate DHs, but this technique is limited by species and genotype recalcitrance. In vivo haploid induction(HI) through seed is widely and efficiently used in maize and was recently extended to several other crops. Here we show that in vivo HI can be triggered by mutation of DMP maternal haploid inducer genes in allopolyploid(allotetraploid) Brassica napus and Nicotiana tabacum. We developed a pipeline for selection of DMP orthologs for clustered regularly interspaced palindromic repeats mutagenesis and demonstrated average amphihaploid induction rates of2.4% and 1.2% in multiple B. napus and N. tabacum genotypes, respectively. These results further confirmed the HI ability of DMP gene in polyploid dicot crops. The DMP-HI system offers a novel DH technology to facilitate breeding in these crops. The success of this approach and the conservation of DMP genes in dicots suggest the broad applicability of this technique in other dicot crops.
基金the National Natural Science Foundation of China(81830053,82001780)Guangzhou Industry-Academia-Research Collaborative Innovation Major Project(201704020015)+2 种基金Natural Science Foundation of Jiangsu Province of China(BK20200361)President Foundation of Nanfang Hospital,Southern Medical University(2017Z012)Distinguished Young Scholars of Gansu Province(20JR10RA713).
文摘Background and Aims:This study aimed to determine the performance of the non-invasive score using noncontrastenhanced MRI(CHESS-DIS score)for detecting portal hy-pertension in cirrhosis.Methods:In this international multicenter,diagnostic study(ClinicalTrials.gov,NCT03766880),patients with cirrhosis who had hepatic venous pressure gradient(HVPG)measurement and noncontrast-enhanced MRI were prospectively recruited from four university hospitals in China(n=4)and Turkey(n=1)between December 2018 and April 2019.A cohort of patients was retrospectively recruited from a university hospital in Italy between March 2015 and November 2017.After segmentation of the liver on fat-suppressed T1-weighted MRI maps,CHESS-DIS score was calculated automatically by an in-house developed code based on the quantification of liver surface nodularity.Results:A total of 149 patients were included,of which 124 were from four Chinese hospitals(training cohort)and 25 were from two international hospitals(validation cohort).A positive correlation between CHESS-DIS score and HVPG was found with the correlation coefficients of 0.36(p<0.0001)and 0.55(p<0.01)for the training and validation cohorts,respectively.The area under the receiver operating characteristic curve of CHESS-DIS score in detection of clinically significant portal hypertension(CSPH)was 0.81 and 0.9 in the training and validation cohorts,respectively.The intra-class correlation coefficients for assessing the inter-and intra-observer agreement were 0.846 and 0.841,respectively.Conclusions:A non-invasive score using noncontrast-enhanced MRI was developed and proved to be significantly correlated with invasive HVPG.Besides,this score could be used to detect CSPH in patients with cirrhosis.
基金the funding support from the National Natural Science Foundation of China(Project No.51571027)the National Environmental Corrosion Platform(NECP)
文摘Corrosion performance of carbon steel in CO_2 aqueous environment containing silty sand with different sizes was investigated by immersion tests and electrochemical measurements.Silty sand could form an adsorption layer on steel surface in initial period,and the sand adsorption layer was turned into a mixture film of silty sand with corrosion product in last period.The adsorption layer in 325 mesh condition(large size)had the fewest pores for H_2CO_3 transport,exhibiting the highest cathodic current inhibition.In spite of little corrosion product,the sand adsorption film formed in 325 mesh condition induced the lowest corrosion rate.For 1000 and 5000 mesh silty sand,the sand adsorption layer had some pores for H_2CO_3 transport,leading to low cathodic current inhibition and much matrix dissolution.But the adsorption layer for5000 mesh silty sand(small size)had the largest special surface area to accelerate heterogeneous precipitation of corrosion product FeCO_3.Therefore,the mixture film in 5000 mesh condition was more compact,exhibiting stronger anodic inhibition and lower corrosion rate than those in 1000 mesh condition.
基金Gansu Science Fund for Distinguished Young Scholars,Grant/Award Number:20JR10RA713Guangxi Digestive Disease Clinical Medical Research Center Construction Project,Grant/Award Number:AD17129027+7 种基金Tianjin Science and Technology Plan Project,Grant/Award Number:19ZXDBSY00030The Xingtai City Science and Technology Project,Grant/Award Number:2020ZZ026Zhejiang Provincial Natural Science Foundation of China,Grant/Award Number:LZ18H180001The Hebei Provincial Health and Family Planning Commission Scientific Research Fund Project,Grant/Award Number:20181612Wenzhou Municipal Science and Technology Bureau,Grant/Award Number:Y2020013National Natural Science Foundation of China,Grant/Award Numbers:81860654,81971713The Hebei Provincial Key R&D Program Project,Grant/Award Number:18277717DNatural Science Foundation of Science and Technology Department of Tibet Autonomous Region,Grant/Award Number:XZ2017ZRG‐91。
文摘Aim:To determine the tolerance and acceptance of hepatic venous pressure gradient(HVPG)measurements in patients with liver cirrhosis.Methods:This prospective international multicenter study included 271 patients with cirrhosis who were scheduled to undergo HVPG measurement between October 2019 and June 2020.Data related to the tolerance and acceptance of HVPG measurements were collected using descriptive questionnaires.Results:HVPG measurements were technically successful in all 271 patients,with 141(52.0%)undergoing HVPG measurement alone.The complication rate was 0.4%.Postoperative pain was significantly lower than preoperative expected pain(p<0.001)and intraoperative pain(p<0.001),and intraoperative pain was also significantly lower than preoperative expected pain(p=0.036).No,mild,moderate,severe,and intolerable discomfort scores were reported by 36.9%,44.6%,11.1%,6.3%,and 0.4%of these patients,respectively,during HVPG measurement and by 54.6%32.5%,11.4%,1.5%,and 0%,respectively,after HVPG measurement.Of these patients,39.5%had little understanding and 10%had no understanding of the value of HVPG measurement,with 35.1%and 4.1%regarding HVPG measurements as being of little or no help,respectively.Most patients reported that they would definitely(15.5%),probably(46.9%),or possibly(29.9%)choose to undergo additional HVPG measurements again,and 62.7%regarded the cost of the procedure as acceptable.Conclusion:HVPG measurement was safe and well‐tolerated in patients with cirrhosis,but patient education and communication are warranted to improve the acceptance of this procedure.
基金Fundo para o Desenvolvimento das Ciências e da Tecnologia(the Science and Technology Development Fund,Macao SAR),Grant/Award Number:FDCT 0060/2020/AGJSpanish Ministry of Health–Instituto de Salud Carlos III,Grant/Award Number:FIS PI20/00220+4 种基金Universidade de Macao(the University of Macao Research Committee),Grant/Award Number:MYRG2020‐00084‐ICMSNatural Science Foundation of Jiangsu Province,Grant/Award Number:BK20200318Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung(the Swiss National Science Foundation),Grant/Award Number:310030_185219&320030_189252the Stiftung für Leberkrankheiten(Swiss Liver Foundation)National Natural Science Foundation of China,Grant/Award Numbers:31961160701,31971309,and 32001069。
文摘Tissue engineering(TE)is promising for the regeneration of failed organs.However,immune rejection,shortage of seed cells,and unintegrated blood vessels restrict the development and clinical application of TE.The last factor is the most challenging and intractable.Harnessing the mature blood vessel network in existing dispensable organs could be a powerful approach to effectively overcome the obstacles.After being remodeled to harbor an immunosuppressive and proregenerative niche,these potential target organs can be transformed into other organs with specific physiological functions,compensating the latter's failed native functions.Organ transformation,such as a hepatized spleen,represents an effective and encouraging TE strategy.In this review,we discuss the current development and obstacles of TE and its feasibility and superiority in organ transformation.
基金National Natural Science Foundation of China,Grant/Award Number:82070588Agenzia Italiana del Farmaco,Ministero della Salute,Grant/Award Number:RF‐2016‐02364358。
文摘Nonalcoholic fatty liver disease(NAFLD)has become the most common chronic liver disease worldwide.NAFLD‐related cirrhosis is often complicated by portal hypertension(PHT).Recent evidence showed that portal venous pressure(PVP)starts to rise in the early stages of NAFLD,even in absence of advanced fibrosis or cirrhosis.However,the precise pathological mechanisms of this process are still poorly understood.Lipid accumulation,hepatocellular ballooning,sinusoidal endothelial cell dysfunction,capillarization,microthrombosis,increased angiogenesis,and pericellular fibrosis may all be involved in the early development of increased PVP in NAFLD.Direct measurement of PHT is invasive and impractical in noncirrhotic NAFLD individuals and may also underestimate its severity.Thus,the development and validation of noninvasive and more accurate measurements,including new serum biomarkers,scoring models,and imaging techniques(such as ultrasonography,elastography,and magnetic resonance imaging),are urgently needed.Owing to the increasing morbidity,challenges in the prevention and management of PHT in NAFLD are unprecedented.This review article aims to briefly discuss these challenges and summarizes the mechanisms,diagnosis,and emerging therapies for PHT in people with NAFLD.
