The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is la...The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.展开更多
Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and ...Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and covalently closed circular DNA(cccDNA)clearance.Serum hepatitis B core-related antigen(HBcrAg)is an emerging HBV marker comprising three components:HBeAg,hepatitis B core antigen,and p22cr.It responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serolo-gical testing.There is a strong correlation,and a decrease in its level corresponds to sustained viral suppression.In patients with chronic hepatitis B(CHB),serum HBcrAg levels are good predictors of HBeAg seroconversion(both spontaneous and after antiviral therapy),particularly in HBeAg-positive patients.Both low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion,which may serve as a good surrogate option for treatment endpoints.In this review,we summarize the role of serum HBcrAg in the treat-ment of CHB.Therefore,long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen,making it a promising marker for monitoring HBV cure.展开更多
BACKGROUND Patients with inflammatory bowel diseases(IBD)often miss the scheduled vaccines and have a higher risk of infection susceptibility,including vaccineprevented diseases.AIM To evaluate the vaccine coverage an...BACKGROUND Patients with inflammatory bowel diseases(IBD)often miss the scheduled vaccines and have a higher risk of infection susceptibility,including vaccineprevented diseases.AIM To evaluate the vaccine coverage and levels of the post-vaccine antibodies against measles,mumps,rubella,and hepatitis B in children with IBD.METHODS Total 98 patients:46 females(47.2%)and 52 males(52.8%)with IBD(Crohn’s disease-75%and ulcerative colitis-25%)with disease onset age-11.0(6.0;14.0)years whom clinical data,vaccination status and levels of the postvaccination antibodies(IgG)for measles,rubella,mumps,hepatitis B,measured with ELISA were prospectively evaluated.The control group consisted of 88 healthy peers from the biobank data.RESULTS Patients with IBD had lower levels of measles,rubella,and hepatitis B,except mumps,compared to controls.Incomplete vaccination/non-protective titer of the antibodies against measles,mumps rubella,and hepatitis B had 33(33.7%)/52.3%,21(21.4%)/50.4%,26(25.8)/25.6%and 26(25.8%)/55.2%,respectively.Patients with incomplete vaccination had a lower age at the diagnosis for all vaccines.The age of the IBD diagnosis≤6 years was the predictor of incomplete vaccination for measles[odds ratio(OR)=4.6,P=0.001],mumps(OR=5.0,P=0.001),rubella(OR=5.4,P=0.0005)and hepatitis B(OR=5.4,P=0.0005)and corticosteroid treatment for measles(OR=2.2,P=0.074)and mumps(OR=3.0,P=0.047)vaccines.Incomplete vaccination was the predictor of nonprotective titer of antibodies against rubella(OR=6.8,95%CI:2.3-19.9,P=0.0002)/mumps(OR=7.0,95%CI:2.4-20.8;P=0.0002).CONCLUSION Patients with IBD had low vaccine coverage and lower levels of anti-vaccine antibodies against measles,rubella,and hepatitis B.Nearly half of the IBD patients require revaccination.展开更多
背景与目的:弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的生发中心B细胞样(germinal center B-cell-like,GCB)亚型和非GCB(non-GCB)亚型在患者预后和治疗上存在差异,但目前依赖有创病理学检查。本研究基于多参数MRI构建...背景与目的:弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的生发中心B细胞样(germinal center B-cell-like,GCB)亚型和非GCB(non-GCB)亚型在患者预后和治疗上存在差异,但目前依赖有创病理学检查。本研究基于多参数MRI构建影像组学和深度学习模型,旨在于术前无创性区分这两种亚型。方法:本研究回顾性分析2013年3月—2024年12月在复旦大学附属华山医院及外院经病理学检查确诊的DLBCL患者。使用多参数MRI扫描数据,结合4种影像组学机器学习[支持向量机(support vector machine,SVM)、逻辑回归(logistic regression,LR)、高斯过程(Gaussian process,GP)和朴素贝叶斯(Naive Bayes,NB)]和3种深度学习[密集连接卷积网络121(densely-connected convolutional networks 121,DenseNet121)、残差网络101(residual network 101,ResNet101)和高效网络B5(Efficient Net-b5)]建立DLBCL亚型分类模型。此外,两名经验不同的放射科医师在盲法下基于MRI图像独立分类DLBCL。模型和医师的诊断性能均通过接收者操作特征曲线下面积(area under the curve,AUC)、准确度(accuracy,ACC)和F1分数(F1-score,F1)等指标进行量化评估,以衡量其区分GCB和non-GCB亚型的能力。本研究经复旦大学附属华山医院伦理委员会批准(KY2024-663),所有患者均知情同意。结果:本研究共纳入173例患者(GCB型55例,non-GCB型118例)。影像组学和深度学习方法能有效地区分DLBCL亚型。其中,GP影像组学模型(基于T1-CE+T2-FLAIR+ADC序列)和DenseNet121深度学习模型(基于T1-CE+T2-FLAIR+ADC序列)表现最佳,在内部验证集上分别取得优异性能(GP:AUC=0.900,ACC=0.896,F1=0.840;DenseNet121:AUC=0.846,ACC=0.854,F1=0.774),并在外部验证集上保持稳健。并且,最优AI模型的分类效能优于经验丰富的放射科医师(医师最高AUC=0.678)。结论:基于多参数MRI特征的影像组学与深度学习模型可有效地鉴别DLBCL的GCB与non-GCB亚型。其中,GP与DenseNet121模型在处理复杂图像数据、特别是融合多序列特征组进行亚型分类时,呈现出优异的性能。展开更多
To improve the economic benefits and farmers’enthusiasm of Brassica napus production,this study compared the agronomic traits,economic traits,and incomes from vegetable and oilseed among five early maturing varieties...To improve the economic benefits and farmers’enthusiasm of Brassica napus production,this study compared the agronomic traits,economic traits,and incomes from vegetable and oilseed among five early maturing varieties of Brassica napus,thereby selecting the suitable materials for breeding the varieties for both vegetable and oil.The results showed that all of the five varieties had low erucic acid in oil and low glucosinolate in rapeseed meal.The economic benefits of the varieties for vegetable and oil were generally higher than those of the varieties for only oil.‘CNT01’had the best economic benefits,with the vegetable yield of 8175.3 kg/hm^(2),the rapeseed yield of 2476.5 kg/hm^(2),the vegetable income of 14859.0 yuan/hm^(2),the rapeseed income of 32701.2 yuan/hm^(2),and the net income of 35560.2 yuan/hm^(2).‘CNZ01’was selected as the variety with highest oil quality,with the rapeseed yield of 2712.6 kg/hm^(2) and the net income of 11775.6 yuan/hm^(2).In conclusion,‘CNT01’was selected as the variety for both vegetable and oil.展开更多
Group B Streptococcus(GBS;Streptococcus agalactiae)is a gram-positive coccus that colonizes the gastrointestinal and genital tracts in adults,as well as the upper respiratory tract in infants.While it has been thought...Group B Streptococcus(GBS;Streptococcus agalactiae)is a gram-positive coccus that colonizes the gastrointestinal and genital tracts in adults,as well as the upper respiratory tract in infants.While it has been thought that GBS only results in invasive disease in pregnant females and neonates,recent literature has suggested an increasing incidence of invasive GBS among non-pregnant individuals within the United States.展开更多
Catalytic asymmetric dearomatization(CADA)has emerged as a powerful strategy for transforming planar aromatic systems into three-dimensional chiral architectures[1].Notably,the Büchner reaction and arene cyclopro...Catalytic asymmetric dearomatization(CADA)has emerged as a powerful strategy for transforming planar aromatic systems into three-dimensional chiral architectures[1].Notably,the Büchner reaction and arene cyclopropanation excel in constructing complex polycyclic frameworks[2].However,current methods predominantly rely on diazo compounds as carbene precursors(Scheme1a),which pose safety risks and limit functional group compatibility.展开更多
The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative ba...The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative bacterial infections,serves as a crucial final recourse against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Nevertheless,the clinical usage of PMB is impeded by its pronounced nephrotoxicity and poor infection site targeting.This investigation is geared to construct a nanoparticle formulation(named HA-PMB@H)comprising hyaluronic acid(HA)and PMB via a simple Schiff base reaction and further coating HA by electrostatic action.HA-PMB@H shows an average size of(153.8±24.3)nm,and a mean zeta potential of(−25.6±5.2)mV.Additionally,PMB can be released from HA-PMB@H more thoroughly and efficiently at pH 5.5 compared to pH 7.4,which demonstrates the Schiff base modification of PMB paves the way for its release at focus of infection.The uptake ratio of HA-PMB@H by alveolar epithelial cells(RLE-6TN)surpassed that of free PMB devoid of HA,which facilitates to the intracellular sterilization of PMB.Furthermore,the employment of HA-PMB@H ameliorated the toxicity of PMB towards human embryonic kidney cells(HEK 293)and pulmonary microvascular endothelial cells(HULEC-5a).What is more,HA-PMB@H effectively managed severe pneumonia induced by CRKP samples from clinical patients diagnosed with CRKP infection in vivo,substantially enhancing the survival rate of mice.Consequently,this nano-delivery system holds promising clinical significance in the combat against drug-resistant bacterial infections.展开更多
BACKGROUND Children with juvenile idiopathic arthritis(JIA)and inflammatory bowel disease(IBD)face an elevated risk of severe infection owing to their diseases and the immunosuppressive treatment for disease control.A...BACKGROUND Children with juvenile idiopathic arthritis(JIA)and inflammatory bowel disease(IBD)face an elevated risk of severe infection owing to their diseases and the immunosuppressive treatment for disease control.AIM To compare scheduled vaccination coverage and the levels of post-vaccine antibodies against measles,mumps,rubella(MMR)and hepatitis B in pediatric patients with IBD and JIA.METHODS A comparative cohort study included 97 patients with IBD and 170 patients with JIA.Vaccination history was obtained from medical records,while post-vaccination immunity was assessed prospectively by measuring specific IgG antibody titers using enzyme-linked immunosorbent assays(Vector-Best JSC,Russia;IBL International,Germany)during routine visits between January 2022 and April 2023.RESULTS A complete two-dose MMR course had been administered to 66.3%of IBD patients and 55.9%of JIA patients(P=0.121).By contrast,the three-dose hepatitis B schedule was completed in 74.2%of IBD and 100%of JIA patients(P<0.001).Protective level of anti-vaccine antibodies against measles(47.7%vs 57.7%;P=0.168);mumps(75.3%vs 80.0%;P=0.366);rubella(74.4%vs 98.2%;P<0.0001);and hepatitis B(44.8%vs 50.0%;P=0.514)were detected in IBD and JIA patients,respectively.CONCLUSION Patients with IBD and JIA demonstrated different vaccination coverage patterns and levels of anti-vaccine antibodies.Routine baseline serology and timely booster vaccination should be implemented for all pediatric patients receiving chronic immunosuppression.展开更多
Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has no...Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.展开更多
BACKGROUND Chronic hepatitis B(CHB)affects>300 million people worldwide.The combi-nation of CHB and cardiometabolic co-morbidities increases the risk of liver-related morbidity and mortality.However,international g...BACKGROUND Chronic hepatitis B(CHB)affects>300 million people worldwide.The combi-nation of CHB and cardiometabolic co-morbidities increases the risk of liver-related morbidity and mortality.However,international guidelines for CHB treatment do not provide recommendations for follow-up examinations or treatment of patients with CHB and cardiometabolic comorbidities.In studies investigating cardiometabolic co-morbidity in patients with CHB,inconsistent findings have been observed,and both lower and higher prevalence of car-diometabolic co-morbidities compared to the general population have been re-ported.It is unclear whether patients with CHB living in Denmark have an increased prevalence of cardiometabolic co-morbidities.We examined patients with CHB and age-,sex-,body mass index(BMI)-,and country-of-birth matched comparison group.Defining cardiometabolic co-morbidity:Obesity(BMI>25 kg/m2/abnormal waist-to-hip ratio),metabolic dysfunction-associated steatotic liver disease(MASLD),hypercholesterolemia(total-cholesterol>5 mmol/L/statin use),hypertension(systolic≥135 mmHg/diastolic≥85 mmHg/antihypertensive medication)and type 2 diabetes(T2D)(2-hour oral glucose tolerance test glucose>11.1 mmol/L/HbA1c>48 mmol/mol/antidiabetic medication).Physical activity was evaluated using maximal oxygen consumption(VO2max),activity monitors,and a questionnaire.RESULTS We included 98 patients with CHB and 49 persons in the comparison group.The two groups were well-matched,showing no significant differences in age,sex,BMI,country-of-birth,education,or employment.Among patients with CHB,the following prevalence of cardiometabolic co-morbidity was found:77%were obese,45%had MASLD,38%had hypercholesterolemia,26%had hypertension,and 7%had T2D,which did not differ significantly from the comparison group,apart from lower prevalence of hemoglobin A1c(HbA1c)≥48 mmol/L or known T2D.Both groups had low VO2max of 27 mL/kg/minute in the patients with CHB and 30 mL/kg/minute in the comparison group,and the patients with CHB had a shorter self-assessed sitting time.CONCLUSION The patients with CHB and the comparison group were well-matched and had a similar prevalence of car-diometabolic comorbidities.Furthermore,both groups had low levels of physical fitness.展开更多
文摘The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.
基金Supported by The Chongqing Talents Project,No.cstc2021ycjh-bgzxm0150The First Batch of Key Disciplines on Public Health in Chongqing,The Health Commission of Chongqing,No.2022(72)+1 种基金The Remarkable Innovation-Clinical Research Project,The Second Affiliated Hospital of Chongqing Medical UniversityThe Scientific and Technological Research Program of Chongqing Municipal Education Commission,the Second Affiliated Hospital of Chongqing Medical University,No.KJZD-K202300404.
文摘Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and covalently closed circular DNA(cccDNA)clearance.Serum hepatitis B core-related antigen(HBcrAg)is an emerging HBV marker comprising three components:HBeAg,hepatitis B core antigen,and p22cr.It responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serolo-gical testing.There is a strong correlation,and a decrease in its level corresponds to sustained viral suppression.In patients with chronic hepatitis B(CHB),serum HBcrAg levels are good predictors of HBeAg seroconversion(both spontaneous and after antiviral therapy),particularly in HBeAg-positive patients.Both low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion,which may serve as a good surrogate option for treatment endpoints.In this review,we summarize the role of serum HBcrAg in the treat-ment of CHB.Therefore,long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen,making it a promising marker for monitoring HBV cure.
文摘BACKGROUND Patients with inflammatory bowel diseases(IBD)often miss the scheduled vaccines and have a higher risk of infection susceptibility,including vaccineprevented diseases.AIM To evaluate the vaccine coverage and levels of the post-vaccine antibodies against measles,mumps,rubella,and hepatitis B in children with IBD.METHODS Total 98 patients:46 females(47.2%)and 52 males(52.8%)with IBD(Crohn’s disease-75%and ulcerative colitis-25%)with disease onset age-11.0(6.0;14.0)years whom clinical data,vaccination status and levels of the postvaccination antibodies(IgG)for measles,rubella,mumps,hepatitis B,measured with ELISA were prospectively evaluated.The control group consisted of 88 healthy peers from the biobank data.RESULTS Patients with IBD had lower levels of measles,rubella,and hepatitis B,except mumps,compared to controls.Incomplete vaccination/non-protective titer of the antibodies against measles,mumps rubella,and hepatitis B had 33(33.7%)/52.3%,21(21.4%)/50.4%,26(25.8)/25.6%and 26(25.8%)/55.2%,respectively.Patients with incomplete vaccination had a lower age at the diagnosis for all vaccines.The age of the IBD diagnosis≤6 years was the predictor of incomplete vaccination for measles[odds ratio(OR)=4.6,P=0.001],mumps(OR=5.0,P=0.001),rubella(OR=5.4,P=0.0005)and hepatitis B(OR=5.4,P=0.0005)and corticosteroid treatment for measles(OR=2.2,P=0.074)and mumps(OR=3.0,P=0.047)vaccines.Incomplete vaccination was the predictor of nonprotective titer of antibodies against rubella(OR=6.8,95%CI:2.3-19.9,P=0.0002)/mumps(OR=7.0,95%CI:2.4-20.8;P=0.0002).CONCLUSION Patients with IBD had low vaccine coverage and lower levels of anti-vaccine antibodies against measles,rubella,and hepatitis B.Nearly half of the IBD patients require revaccination.
文摘背景与目的:弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)的生发中心B细胞样(germinal center B-cell-like,GCB)亚型和非GCB(non-GCB)亚型在患者预后和治疗上存在差异,但目前依赖有创病理学检查。本研究基于多参数MRI构建影像组学和深度学习模型,旨在于术前无创性区分这两种亚型。方法:本研究回顾性分析2013年3月—2024年12月在复旦大学附属华山医院及外院经病理学检查确诊的DLBCL患者。使用多参数MRI扫描数据,结合4种影像组学机器学习[支持向量机(support vector machine,SVM)、逻辑回归(logistic regression,LR)、高斯过程(Gaussian process,GP)和朴素贝叶斯(Naive Bayes,NB)]和3种深度学习[密集连接卷积网络121(densely-connected convolutional networks 121,DenseNet121)、残差网络101(residual network 101,ResNet101)和高效网络B5(Efficient Net-b5)]建立DLBCL亚型分类模型。此外,两名经验不同的放射科医师在盲法下基于MRI图像独立分类DLBCL。模型和医师的诊断性能均通过接收者操作特征曲线下面积(area under the curve,AUC)、准确度(accuracy,ACC)和F1分数(F1-score,F1)等指标进行量化评估,以衡量其区分GCB和non-GCB亚型的能力。本研究经复旦大学附属华山医院伦理委员会批准(KY2024-663),所有患者均知情同意。结果:本研究共纳入173例患者(GCB型55例,non-GCB型118例)。影像组学和深度学习方法能有效地区分DLBCL亚型。其中,GP影像组学模型(基于T1-CE+T2-FLAIR+ADC序列)和DenseNet121深度学习模型(基于T1-CE+T2-FLAIR+ADC序列)表现最佳,在内部验证集上分别取得优异性能(GP:AUC=0.900,ACC=0.896,F1=0.840;DenseNet121:AUC=0.846,ACC=0.854,F1=0.774),并在外部验证集上保持稳健。并且,最优AI模型的分类效能优于经验丰富的放射科医师(医师最高AUC=0.678)。结论:基于多参数MRI特征的影像组学与深度学习模型可有效地鉴别DLBCL的GCB与non-GCB亚型。其中,GP与DenseNet121模型在处理复杂图像数据、特别是融合多序列特征组进行亚型分类时,呈现出优异的性能。
文摘To improve the economic benefits and farmers’enthusiasm of Brassica napus production,this study compared the agronomic traits,economic traits,and incomes from vegetable and oilseed among five early maturing varieties of Brassica napus,thereby selecting the suitable materials for breeding the varieties for both vegetable and oil.The results showed that all of the five varieties had low erucic acid in oil and low glucosinolate in rapeseed meal.The economic benefits of the varieties for vegetable and oil were generally higher than those of the varieties for only oil.‘CNT01’had the best economic benefits,with the vegetable yield of 8175.3 kg/hm^(2),the rapeseed yield of 2476.5 kg/hm^(2),the vegetable income of 14859.0 yuan/hm^(2),the rapeseed income of 32701.2 yuan/hm^(2),and the net income of 35560.2 yuan/hm^(2).‘CNZ01’was selected as the variety with highest oil quality,with the rapeseed yield of 2712.6 kg/hm^(2) and the net income of 11775.6 yuan/hm^(2).In conclusion,‘CNT01’was selected as the variety for both vegetable and oil.
文摘Group B Streptococcus(GBS;Streptococcus agalactiae)is a gram-positive coccus that colonizes the gastrointestinal and genital tracts in adults,as well as the upper respiratory tract in infants.While it has been thought that GBS only results in invasive disease in pregnant females and neonates,recent literature has suggested an increasing incidence of invasive GBS among non-pregnant individuals within the United States.
文摘Catalytic asymmetric dearomatization(CADA)has emerged as a powerful strategy for transforming planar aromatic systems into three-dimensional chiral architectures[1].Notably,the Büchner reaction and arene cyclopropanation excel in constructing complex polycyclic frameworks[2].However,current methods predominantly rely on diazo compounds as carbene precursors(Scheme1a),which pose safety risks and limit functional group compatibility.
基金supported by the National Natural Science Foundation of China(Nos.81860543,32360237)Guizhou Provincial Science and Technology Projects(Nos.ZK[2024]235,ZK[2023]Key Project 041).
文摘The escalation in the incidence of multidrug-resistant Gram-negative bacteria is becoming a pressing global concern.Polymyxin B(PMB),a conventional antibiotic with notable therapeutic efficacy against Gram-negative bacterial infections,serves as a crucial final recourse against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Nevertheless,the clinical usage of PMB is impeded by its pronounced nephrotoxicity and poor infection site targeting.This investigation is geared to construct a nanoparticle formulation(named HA-PMB@H)comprising hyaluronic acid(HA)and PMB via a simple Schiff base reaction and further coating HA by electrostatic action.HA-PMB@H shows an average size of(153.8±24.3)nm,and a mean zeta potential of(−25.6±5.2)mV.Additionally,PMB can be released from HA-PMB@H more thoroughly and efficiently at pH 5.5 compared to pH 7.4,which demonstrates the Schiff base modification of PMB paves the way for its release at focus of infection.The uptake ratio of HA-PMB@H by alveolar epithelial cells(RLE-6TN)surpassed that of free PMB devoid of HA,which facilitates to the intracellular sterilization of PMB.Furthermore,the employment of HA-PMB@H ameliorated the toxicity of PMB towards human embryonic kidney cells(HEK 293)and pulmonary microvascular endothelial cells(HULEC-5a).What is more,HA-PMB@H effectively managed severe pneumonia induced by CRKP samples from clinical patients diagnosed with CRKP infection in vivo,substantially enhancing the survival rate of mice.Consequently,this nano-delivery system holds promising clinical significance in the combat against drug-resistant bacterial infections.
文摘BACKGROUND Children with juvenile idiopathic arthritis(JIA)and inflammatory bowel disease(IBD)face an elevated risk of severe infection owing to their diseases and the immunosuppressive treatment for disease control.AIM To compare scheduled vaccination coverage and the levels of post-vaccine antibodies against measles,mumps,rubella(MMR)and hepatitis B in pediatric patients with IBD and JIA.METHODS A comparative cohort study included 97 patients with IBD and 170 patients with JIA.Vaccination history was obtained from medical records,while post-vaccination immunity was assessed prospectively by measuring specific IgG antibody titers using enzyme-linked immunosorbent assays(Vector-Best JSC,Russia;IBL International,Germany)during routine visits between January 2022 and April 2023.RESULTS A complete two-dose MMR course had been administered to 66.3%of IBD patients and 55.9%of JIA patients(P=0.121).By contrast,the three-dose hepatitis B schedule was completed in 74.2%of IBD and 100%of JIA patients(P<0.001).Protective level of anti-vaccine antibodies against measles(47.7%vs 57.7%;P=0.168);mumps(75.3%vs 80.0%;P=0.366);rubella(74.4%vs 98.2%;P<0.0001);and hepatitis B(44.8%vs 50.0%;P=0.514)were detected in IBD and JIA patients,respectively.CONCLUSION Patients with IBD and JIA demonstrated different vaccination coverage patterns and levels of anti-vaccine antibodies.Routine baseline serology and timely booster vaccination should be implemented for all pediatric patients receiving chronic immunosuppression.
基金supported by the National Natural Science Foundation of China(82270479,82070460)the Beijing Natural Science Foundation(7242084 to Xun-De Xian)the National Key Research and Development Program of China from the Ministry of Science and Technology(2021YFF0702802 to Yu-Hui Wang).
文摘Background:Kinesin family member 13B(KIF13B),a crucial motor protein,exerts multiple cellular biological functions.However,the implication of KIF13B in metabolic dysfunction-associated fatty liver disease(MAFLD)has not been explored yet.This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target.Methods:We assessed KIF13B expression in MAFLD patients and rodent models.The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice,hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets.The underlying mechanisms by which Kif13bgoverned hepatic lipid homeostasis and MAFLD progression were explored in vitro.Finally,the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD.Results:KIF13B expression was reduced in patients and murine models with MAFLD.Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis,which is further exacerbated by different overnutrition diets.Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis(MASH)in methionine-choline-deficient diet(MCD)-fed mice.Furthermore,Kif13b deficiency accelerates atherosclerosis in the context of MAFLD.Mechanistically,Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation.Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1(AMPKα1)to regulate the phosphorylation of AMPKα1,governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1(Srebp1)-mediated denovo lipogenesis in the liver.Conclusion:This work establishes a causal relationship between KIF13B deficiency and MAFLD,emphasizing KIF13B as a potential therapeutic target for treating MAFLD.
基金Supported by The Centre for Physical Activity Research(CFAS),TrygFonden,No.125132and The Beckett Foundation,No.22-2-9924.
文摘BACKGROUND Chronic hepatitis B(CHB)affects>300 million people worldwide.The combi-nation of CHB and cardiometabolic co-morbidities increases the risk of liver-related morbidity and mortality.However,international guidelines for CHB treatment do not provide recommendations for follow-up examinations or treatment of patients with CHB and cardiometabolic comorbidities.In studies investigating cardiometabolic co-morbidity in patients with CHB,inconsistent findings have been observed,and both lower and higher prevalence of car-diometabolic co-morbidities compared to the general population have been re-ported.It is unclear whether patients with CHB living in Denmark have an increased prevalence of cardiometabolic co-morbidities.We examined patients with CHB and age-,sex-,body mass index(BMI)-,and country-of-birth matched comparison group.Defining cardiometabolic co-morbidity:Obesity(BMI>25 kg/m2/abnormal waist-to-hip ratio),metabolic dysfunction-associated steatotic liver disease(MASLD),hypercholesterolemia(total-cholesterol>5 mmol/L/statin use),hypertension(systolic≥135 mmHg/diastolic≥85 mmHg/antihypertensive medication)and type 2 diabetes(T2D)(2-hour oral glucose tolerance test glucose>11.1 mmol/L/HbA1c>48 mmol/mol/antidiabetic medication).Physical activity was evaluated using maximal oxygen consumption(VO2max),activity monitors,and a questionnaire.RESULTS We included 98 patients with CHB and 49 persons in the comparison group.The two groups were well-matched,showing no significant differences in age,sex,BMI,country-of-birth,education,or employment.Among patients with CHB,the following prevalence of cardiometabolic co-morbidity was found:77%were obese,45%had MASLD,38%had hypercholesterolemia,26%had hypertension,and 7%had T2D,which did not differ significantly from the comparison group,apart from lower prevalence of hemoglobin A1c(HbA1c)≥48 mmol/L or known T2D.Both groups had low VO2max of 27 mL/kg/minute in the patients with CHB and 30 mL/kg/minute in the comparison group,and the patients with CHB had a shorter self-assessed sitting time.CONCLUSION The patients with CHB and the comparison group were well-matched and had a similar prevalence of car-diometabolic comorbidities.Furthermore,both groups had low levels of physical fitness.
