AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyse...AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyses were performed on a Chinese family with two affected siblings.Whole-exome sequencing(WES)was conducted for the proband and other family members.Bioinformatics tools were used to evaluate the conservation,predicted pathogenicity,and structural effects of the identified ADAMTS17 variants.In addition,protein structure modeling was applied to assess the functional impacts of the mutations.RESULTS:The proband(a 32-year-old male)and his elder sister(42y)presented typical clinical features of WMS,including short stature,brachydactyly,high myopia,ectopia lentis,and secondary glaucoma.WES identified a novel compound heterozygous mutation in ADAMTS17:a splicing mutation(c.451-2A>G)inherited from the father and a missense mutation(c.1043G>A;p.C348Y)inherited from the mother.The splicing mutation disrupted normal mRNA splicing and processing,leading to premature translation termination.The missense mutation,which is located in the metalloprotease catalytic domain,was predicted to abolish a critical disulfide bond,thereby impairing protein stability.Both mutations exhibited high evolutionary conservation and were predicted to be pathogenic by multiple bioinformatics algorithms.CONCLUSION:A novel compound heterozygous mutation in ADAMTS17 is identified in this WMS-affected Chinese family,and its pathogenicity is verified via bioinformatics analysis and protein structural modeling.These findings are expected to facilitate the genetic diagnosis of WMS and deepen the understanding of its molecular pathogenesis.展开更多
BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such a...BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.展开更多
In this paper, we focused on numerical solutions of carcinogenesis mutations models that are based on reaction-diffusion systems and Lotka-Volterra food chains. We consider the case with one and two-stages of mutation...In this paper, we focused on numerical solutions of carcinogenesis mutations models that are based on reaction-diffusion systems and Lotka-Volterra food chains. We consider the case with one and two-stages of mutations with appropriate initial conditions and the zero-flux boundary conditions. The main purpose is to construct a stable discretization scheme, which allows much accuracy than those of a standard approach. To this end, we use the spectral method to postprocess numerical solutions for the proposed model by using some classical methods for solving differential equations. The implementation of the algorithm is simple and it does not need to solve the linear or nonlinear system (in case the model is nonlinear). We simulate the one and two-stage carcinogenesis mutations model and compared the results with previously published ones.展开更多
Bacillus megaterium as a companion strain in two-stage fermentation of vitamin C could secrete some active substances to spur growth of Gluconobacter oxydans to produce 2-KLG. In the fermenting system where Gluconobac...Bacillus megaterium as a companion strain in two-stage fermentation of vitamin C could secrete some active substances to spur growth of Gluconobacter oxydans to produce 2-KLG. In the fermenting system where Gluconobacter oxydans was combined with GB82-a mutated strain of B. megaterium by ion implantation, the amount of 2-KLG harvested was larger than that produced by the original B. megaterium BP52 being substituted for GB82. In this paper, we studied the effect of the active substances secreted by GB82 to enhance the capability of Gluconobacter oxydans to produce 2-KLG. The supernate of GB82 sampled at different cultivation times all had much more activity to spur Gluconobacter oxydans to yield 2-KLG than that of the original B. megaterium, which might be due to the genetic changes in the active components caused by ion implantation. Furthermore, the active substances of GB82's supernate would lose a part of its activity in extreme environments, which is typical of some proteins.展开更多
BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),w...BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),with its noninvasive capability to assess tumor characteristics in detail,has shown promise in evaluating treatment response and predicting therapeutic outcomes.This technology holds potential for guiding personalized treatment strategies tailored to individual patient profiles,enhancing the precision and effectiveness of colorectal cancer care.AIM To create a multiparametric MRI-based predictive model for assessing chemotherapy efficacy in colorectal cancer patients with gene mutations.METHODS This retrospective study was conducted in a tertiary hospital,analyzing 157 colorectal cancer patients with gene mutations treated between August 2022 and December 2023.Based on chemotherapy outcomes,the patients were categorized into favorable(n=60)and unfavorable(n=50)response groups.Univariate and multivariate logistic regression analyses were performed to identify independent predictors of chemotherapy efficacy.A predictive nomogram was constructed using significant variables,and its performance was assessed using the area under the receiver operating characteristic curve(AUC)in both training and validation sets.RESULTS Univariate analysis identified that tumor differentiation,T2 signal intensity ratio,tumor-to-anal margin distance,and MRI-detected lymph node metastasis as significantly associated with chemotherapy response(P<0.05).Multivariate Logistics regression confirmed these four parameters as independent predictors.The predictive model demonstrated strong discrimination,with an AUC of 0.938(sensitivity:86%;specificity:92%)in the training set,and 0.942(sensitivity:100%;specificity:83%)in the validation set.CONCLUSION We established and validated a multiparametric MRI-based model for predicting chemotherapy response in colorectal cancer patients with gene mutations.This model holds promise for guiding individualized treatment strategies.展开更多
Inbreeding increases genome homozygosity within populations,which can exacerbate inbreeding depression by exposing homozygous deleterious alleles that are responsible for declines in fitness traits.In small population...Inbreeding increases genome homozygosity within populations,which can exacerbate inbreeding depression by exposing homozygous deleterious alleles that are responsible for declines in fitness traits.In small populations,genetic purging that occurs under the pressure of natural selection acts as an opposing force,contributing to a reduction of deleterious alleles.Both inbreeding and genetic purging are paramount in the field of conservation genomics.The Amur tiger(Panthera tigris altaica)lives in small populations in the forests of Northeast Asia and is among the most endangered animals on the planet.Using genome-wide assessment and comparison,we reveal substantially higher and more extensive inbreeding in wild Amur tigers(F_(ROH)=0.50)than in captive individuals(F_(ROH)=0.24).However,a relatively reduced number of lossof-function mutations in wild Amur tigers is observed compared to captive individuals,indicating genetic purging of inbreeding load with relatively large-effect alleles.The higher ratio of homozygous mutation load and number of fixed damaging alleles in the wild population indicates a less-efficient genetic purging,with purifying selection also contributing to this process.These findings provide valuable insights for the future conservation of Amur tigers.展开更多
A new unified constitutive model was developed to predict the two-stage creep-aging(TSCA)behavior of Al-Zn-Mg-Cu alloys.The particular bimodal precipitation feature was analyzed and modeled by considering the primary ...A new unified constitutive model was developed to predict the two-stage creep-aging(TSCA)behavior of Al-Zn-Mg-Cu alloys.The particular bimodal precipitation feature was analyzed and modeled by considering the primary micro-variables evolution at different temperatures and their interaction.The dislocation density was incorporated into the model to capture the effect of creep deformation on precipitation.Quantitative transmission electron microscopy and experimental data obtained from a previous study were used to calibrate the model.Subsequently,the developed constitutive model was implemented in the finite element(FE)software ABAQUS via the user subroutines for TSCA process simulation and the springback prediction of an integral panel.A TSCA test was performed.The result shows that the maximum radius deviation between the formed plate and the simulation results is less than 0.4 mm,thus validating the effectiveness of the developed constitutive model and FE model.展开更多
BACKGROUND Thrombophilia contributes to a significant increased risk of venous thromboembolism and can be either inherited or acquired.Hereditary thrombophilia may arise from various gene mutations,some of which have ...BACKGROUND Thrombophilia contributes to a significant increased risk of venous thromboembolism and can be either inherited or acquired.Hereditary thrombophilia may arise from various gene mutations,some of which have not even been adequately reported or poorly understood.Previous studies reported a rare and novel missense mutation in the prothrombin gene(p.Arg596Gln),known as prothrombin Belgrade.The mechanisms and therapeutic strategies associated with prothrombin Belgrade mutation have not been fully elucidated.CASE SUMMARY We present the case of a 26-year-old woman with recurrent systemic thrombosis induced by prothrombin Belgrade mutation.The patient suffered from cerebral venous sinus thrombosis that rapidly progressed to systemic thrombosis,alongside a family history of cerebral thrombosis,and no traditional risk factors or abnormal coagulation function.Whole-genome sequencing detected a novel and rare heterozygous prothrombin missense mutation,c.1787G>T(p.Arg596Gln),which was responsible for the major etiology of the systemic thrombosis.CONCLUSION This case strengthens our understanding about hereditary basis of thrombophilia and provokes considerations for therapeutic options on prothrombin Belgrade mutation.展开更多
BACKGROUND Through deeper understanding of targetable driver mutations in non-small-cell lung cancer(NSCLC)over the past years,some patients with driver mutations have benefited from the targeted molecular therapies.A...BACKGROUND Through deeper understanding of targetable driver mutations in non-small-cell lung cancer(NSCLC)over the past years,some patients with driver mutations have benefited from the targeted molecular therapies.Although the anaplastic lymphoma kinase and BRAF mutations are not frequent subtypes in NSCLC,the availability of several targeted-drugs has been confirmed through a series of clinical trials.But little is clear about the proper strategy in rare BRAF G469A mutation,not to mention co-exhibition of anaplastic lymphoma kinase and BRAF G469A mutations,which is extremely rare in NSCLC.CASE SUMMARY We present a patient to stage IVA lung adenocarcinoma with coexisting echinoderm microtubule associated protein like-4 rearrangement and BRAF G469A mutation.She received several targeted drugs with unintended resistance and suffered from unbearable adverse events.CONCLUSION Due to the rarity of co-mutations,the case not only enriches the limited literature on NSCLC harbouring BRAF G469A and echinoderm microtubule associated protein like-4 mutations,but also suggests the efficacy and safety of specific multiple-drug therapy in such patients.展开更多
Objective:Keratoconus(KC)is a progressive corneal ectasia disorder,arising from a myriad of causes including genetic predispositions,environmental factors,biomechanical influences,and inflammatory reactions.This study...Objective:Keratoconus(KC)is a progressive corneal ectasia disorder,arising from a myriad of causes including genetic predispositions,environmental factors,biomechanical influences,and inflammatory reactions.This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population.Methods:Twenty-five patients with primary KC as well as 50 unrelated population matched healthy controls,were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population.Sanger sequencing and whole-exome sequencing(WES)were used to analyze mutations in the zinc finger protein 469(ZNF469)gene.Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis.Results:Five novel heterozygous missense variants were identified in KC patients.Among them,2 compound heterozygous variants,c.8986G>C(p.E2996Q)with c.11765A>C(p.D3922A),and c.4423C>G(p.L1475V)with c.10633G>A(p.G3545R),were determined to be possible pathogenic factors for KC.Conclusion:Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population.These mutation sites may provide valuable information for future genetic screening of KC patients and their families.展开更多
Sotos syndrome is characterized by overgrowth features and is caused by alterations in the nuclear receptor binding SET domain protein 1 gene.Attentiondeficit/hyperactivity disorder(ADHD)is considered a neurodevelopme...Sotos syndrome is characterized by overgrowth features and is caused by alterations in the nuclear receptor binding SET domain protein 1 gene.Attentiondeficit/hyperactivity disorder(ADHD)is considered a neurodevelopment and psychiatric disorder in childhood.Genetic characteristics and clinical presentation could play an important role in the diagnosis of Sotos syndrome and ADHD.Magnetic resonance imaging(MRI)has been used to assess medical images in Sotos syndrome and ADHD.The images process is considered to display in MRI while wavelet fusion has been used to integrate distinct images for achieving more complete information in single image in this editorial.In the future,genetic mechanisms and artificial intelligence related to medical images could be used in the clinical diagnosis of Sotos syndrome and ADHD.展开更多
BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qua...BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qualitatively various protein activities,which may be reflected in their differential association with tumor characteristics.AIM To examine the association between these mutations and colorectal cancer(CRC)progression stages.METHODS A retrospective analysis was conducted on 799 patients with CRC,whose tumor samples were examined for mutations in the hot-spots of the KRAS,NRAS,and BRAF genes at the University of Texas Medical Branch,spanning from January 2016 to July 2023.Statistical analyses were performed to assess the association of spe-cific nucleotide changes with tumor,nodes,and metastasis stages.RESULTS KRAS mutations were found in 39.5%of cases,NRAS mutations in 4.4%,and BRAF mutations in 6.0%.The KRAS p.Gly12Val and p.Gly13Asp mutations were positively associated with pathological stage 4 tumors.Additionally,the KRAS p.Gly12Asp and p.Gly12Val mutations were linked to an increased risk of distant metastasis.Meanwhile,the BRAF Val600Glu mutation was associated with a higher likelihood of lymph node involvement.CONCLUSION Our findings support the potential prognostic utility of specific KRAS(p.Gly12Val,p.Gly12Asp,and p.Gly13Asp)and BRAF p.Val600Glu mutations in CRC.These results are preliminary and require validation through larger,multi-center studies before they can be considered reliable in clinical practice.展开更多
BACKGROUND Only a few cases of diabetes mellitus with concurrent mutations in the mitochondrial MT-TL1 and CEL genes have been reported worldwide.Racial differences may influence mutation frequency,the presentation of...BACKGROUND Only a few cases of diabetes mellitus with concurrent mutations in the mitochondrial MT-TL1 and CEL genes have been reported worldwide.Racial differences may influence mutation frequency,the presentation of symptoms,and disease progression.This case report describes the clinical features,potential genetic mechanisms,and diagnostic complexity of young-onset diabetes mellitus with concurrent m.3243A>G mutation in MT-TL1 and c.1336G>A mutation in CEL.The objective is to inform precise typing,genetic counseling,and personalized treatment of monogenic diabetes mellitus,while expanding the evidence base on rare forms of diabetes mellitus.CASE SUMMARY A 30-year-old man,diagnosed with diabetic ketoacidosis six years earlier,presented with poor response to insulin therapy(glycated hemoglobin,15.35%),marked wasting(body mass index:15.06 kg/m2),sensorineural deafness,diabetic retinopathy,and peripheral neuropathy.Whole-exome sequencing revealed concurrent mutations:Mitochondrial MT-TL1 m.3243A>G(heteroplasmy 41.76%)and CEL c.1336G>A.Family investigation identified his mother,who also had diabetes,as a carrier of the CEL mutation,and his sister as harboring both mutations without diabetes.CONCLUSION This case highlights the genetic heterogeneity of monogenic diabetes and expands the known mutational spectrum.Comprehensive genetic testing is recommended to enhance diagnostic accuracy in cases of suspected monogenic diabetes.展开更多
Lexical analysis is a fundamental task in natural language processing,which involves several subtasks,such as word segmentation(WS),part-of-speech(POS)tagging,and named entity recognition(NER).Recent works have shown ...Lexical analysis is a fundamental task in natural language processing,which involves several subtasks,such as word segmentation(WS),part-of-speech(POS)tagging,and named entity recognition(NER).Recent works have shown that taking advantage of relatedness between these subtasks can be beneficial.This paper proposes a unified neural framework to address these subtasks simultaneously.Apart from the sequence tagging paradigm,the proposed method tackles the multitask lexical analysis via two-stage sequence span classification.Firstly,the model detects the word and named entity boundaries by multilabel classification over character spans in a sentence.Then,the authors assign POS labels and entity labels for words and named entities by multi-class classification,respectively.Furthermore,a Gated Task Transformation(GTT)is proposed to encourage the model to share valuable features between tasks.The performance of the proposed model was evaluated on Chinese and Thai public datasets,demonstrating state-of-the-art results.展开更多
Applying bio-oxidation waste solution(BOS)to chemical-biological two-stage oxidation process can significantly improve the bio-oxidation efficiency of arsenopyrite.This study aims to clarify the enhanced oxidation mec...Applying bio-oxidation waste solution(BOS)to chemical-biological two-stage oxidation process can significantly improve the bio-oxidation efficiency of arsenopyrite.This study aims to clarify the enhanced oxidation mechanism of arsenopyrite by evaluating the effects of physical and chemical changes of arsenopyrite in BOS chemical oxidation stage on mineral dissolution kinetics,as well as microbial growth activity and community structure composition in bio-oxidation stage.The results showed that the chemical oxidation contributed to destroying the physical and chemical structure of arsenopyrite surface and reducing the particle size,and led to the formation of nitrogenous substances on mineral surface.These chemical oxidation behaviors effectively promoted Fe^(3+)cycling in the bio-oxidation system and weakened the inhibitory effect of the sulfur film on ionic diffusion,thereby enhancing the dissolution kinetics of the arsenopyrite.Therefore,the bio-oxidation efficiency of arsenopyrite was significantly increased in the two-stage oxidation process.After 18 d,the two-stage oxidation process achieved total extraction rates of(88.8±2.0)%,(86.7±1.3)%,and(74.7±3.0)%for As,Fe,and S elements,respectively.These values represented a significant increase of(50.8±3.4)%,(47.1±2.7)%,and(46.0±0.7)%,respectively,compared to the one-stage bio-oxidation process.展开更多
Objective:To investigate the clinical and molecular genetic characteristics of Chinese adolescents with maturity-onset diabetes of the young type 2(MODY 2)and the safety and efficacy of recombinant human growth hormon...Objective:To investigate the clinical and molecular genetic characteristics of Chinese adolescents with maturity-onset diabetes of the young type 2(MODY 2)and the safety and efficacy of recombinant human growth hormone(r-hGH).Methods:The clinical features and laboratory data of a family with MODY 2 combined with partial growth hormone deficiency(pGHD),diagnosed at the Fourth Clinical Medical College of Xinjiang Medical University,were analyzed.DNA was extracted from peripheral blood using the column method,and Sanger sequencing was conducted to analyze the glucokinase(GCK),hepatocyte nuclear factor 1α(HNF1α),and hepatocyte nuclear factor 4α(HNF4α)in the proband and relevant family members.Results:A heterozygous mutation in GCK(Reference sequence:NM_000162,location:Exon 10)c.1340G>A(p.R447Q)was detected in three family members(the proband,the proband’s younger brother,and their mother).The proband also had pGHD.Conclusion:GCK mutations causing MODY 2 exist in the Chinese population,and the combined treatment with r-hGH is safe and effective.展开更多
Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in viv...Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.展开更多
Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(...Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(SSB1 and SSB2).However,the functional divergence of these two SSB copies in plants remains largely unknown,and detailed studies regarding their roles in the replication and recombination of organellar genomes are still incomplete.In this study,phylogenetic,gene structure and protein motif analyses all suggested that SSB1 and SSB2 probably diverged during the early evolution of seed plants.Based on accurate long-read sequencing results,ssb1 and ssb2 mutants had decreased copy numbers for both mitochondrial DNA(mtDNA)and plastid DNA(ptDNA),accompanied by a slight increase in structural rearrangements mediated by intermediate-sized repeats in mt genome and small-scale variants in both genomes.Our findings provide an important foundation for further investigating the effects of DNA dosage in the regulation of mutation frequencies in plant organellar genomes.展开更多
Exploring the factors driving the decoupling of China’s sulfur dioxide(SO_(2))emissions from economic growth(DEI)is crucial for achieving sustainable development.By analyzing the decoupling indicators and driving fac...Exploring the factors driving the decoupling of China’s sulfur dioxide(SO_(2))emissions from economic growth(DEI)is crucial for achieving sustainable development.By analyzing the decoupling indicators and driving factors at both the generation and treatment stages of SO_(2),more effective targeted mitigation strategies can be developed.We employ the Tapio decoupling model and propose a two-stage method to examine the decoupling issues related to SO_(2).Our findings indicate that:①DEI shows a steady and significant improvement,with SO_(2)emission intensity identified as the primary driver.②for the decoupling of economic growth and SO_(2)generation,energy scale serves as the largest stimulator,while the effect of energy intensity changes from negative to positive,and pollution intensity is first positive and then negative.③For the decoupling of SO_(2)generation and SO_(2)removal,treatment efficiency leads as the largest promoter,followed by treatment intensity.Based on these results,this study recommends that China focuses more on enhancing clean energy utilization and the effectiveness of treatment processes.展开更多
BACKGROUND Two-stage revision is the most common treatment for chronic periprosthetic joint infection of the hip,involving a resection arthroplasty with or without placement of an antibiotic-loaded spacer,followed by ...BACKGROUND Two-stage revision is the most common treatment for chronic periprosthetic joint infection of the hip,involving a resection arthroplasty with or without placement of an antibiotic-loaded spacer,followed by antibiotic therapy before reimplantation.AIM To compare the outcomes and complications of two consecutive treatment protocols for two-stage revision arthroplasty of the infected hip:One using Girdlestone with an antibiotic holiday,the other using custom-made articulating spacers(CUMARS)without an antibiotic holiday.METHODS In this retrospective study,two consecutive cohorts were compared.Group A(2017-2020)underwent two-stage revision with a Girdlestone and an antibiotic holiday before reimplantation,while Group B(2020-2023)received CUMARS whenever possible,and no antibiotic holiday,or a Girdlestone if indicated.The primary outcome was successful infection eradication after one year.Secondary outcomes included surgical duration,length of hospital stay,weight-bearing allowance,discharge destination,and complications.RESULTS A total of 98 patients were included:39 patients in Group A and 59 patients in Group B.Successful infection eradication after one year was achieved in 69%of Group A and 83%of Group B(P=0.164).Patients in Group B were more frequently allowed to bear weight(64%vs 18%,P<0.001),had a shorter in-hospital stay(9 vs 16 days,P<0.001),and were more often discharged home after the first surgery(48%vs 24%,P=0.048).No significant differences were found in(mechanical)complications.CONCLUSION A protocol including CUMARS is a safe and effective treatment,offering faster recovery,shorter length of hospital stay,and enabling more patients to return home during the interval.This reduces strain on patients and the healthcare system,potentially saving costs,without compromising infection control or increasing(mechanical)complications.展开更多
文摘AIM:To investigate the genetic basis of Weill-Marchesani syndrome(WMS)in a Chinese family and clarify the pathogenic mechanism of novel ADAMTS17 mutations.METHODS:Comprehensive clinical assessments and genetic analyses were performed on a Chinese family with two affected siblings.Whole-exome sequencing(WES)was conducted for the proband and other family members.Bioinformatics tools were used to evaluate the conservation,predicted pathogenicity,and structural effects of the identified ADAMTS17 variants.In addition,protein structure modeling was applied to assess the functional impacts of the mutations.RESULTS:The proband(a 32-year-old male)and his elder sister(42y)presented typical clinical features of WMS,including short stature,brachydactyly,high myopia,ectopia lentis,and secondary glaucoma.WES identified a novel compound heterozygous mutation in ADAMTS17:a splicing mutation(c.451-2A>G)inherited from the father and a missense mutation(c.1043G>A;p.C348Y)inherited from the mother.The splicing mutation disrupted normal mRNA splicing and processing,leading to premature translation termination.The missense mutation,which is located in the metalloprotease catalytic domain,was predicted to abolish a critical disulfide bond,thereby impairing protein stability.Both mutations exhibited high evolutionary conservation and were predicted to be pathogenic by multiple bioinformatics algorithms.CONCLUSION:A novel compound heterozygous mutation in ADAMTS17 is identified in this WMS-affected Chinese family,and its pathogenicity is verified via bioinformatics analysis and protein structural modeling.These findings are expected to facilitate the genetic diagnosis of WMS and deepen the understanding of its molecular pathogenesis.
文摘BACKGROUND Early renal artery thrombosis after kidney transplantation is rare but often leads to graft loss.Prompt diagnosis and intervention are essential,particularly in patients with inherited thrombophilias such as factor V Leiden(FVL)mutation.CASE SUMMARY A kidney transplant recipient with FVL mutation developed an acute transplant renal artery thrombosis.The immediate post-operative Doppler ultrasonography revealed thrombosis of the main and inferior polar renal arteries.Emergent thrombectomy and separate arterial re-anastomoses were performed after cold perfusion with heparinized saline and vasodilator solution.Reperfusion was successful with immediate urine output and gradual improvement in renal function.The patient was discharged on direct oral anticoagulation therapy.CONCLUSION Early detection and surgical intervention can preserve graft function in posttransplant renal artery thrombosis even in patients at high risk.
文摘In this paper, we focused on numerical solutions of carcinogenesis mutations models that are based on reaction-diffusion systems and Lotka-Volterra food chains. We consider the case with one and two-stages of mutations with appropriate initial conditions and the zero-flux boundary conditions. The main purpose is to construct a stable discretization scheme, which allows much accuracy than those of a standard approach. To this end, we use the spectral method to postprocess numerical solutions for the proposed model by using some classical methods for solving differential equations. The implementation of the algorithm is simple and it does not need to solve the linear or nonlinear system (in case the model is nonlinear). We simulate the one and two-stage carcinogenesis mutations model and compared the results with previously published ones.
文摘Bacillus megaterium as a companion strain in two-stage fermentation of vitamin C could secrete some active substances to spur growth of Gluconobacter oxydans to produce 2-KLG. In the fermenting system where Gluconobacter oxydans was combined with GB82-a mutated strain of B. megaterium by ion implantation, the amount of 2-KLG harvested was larger than that produced by the original B. megaterium BP52 being substituted for GB82. In this paper, we studied the effect of the active substances secreted by GB82 to enhance the capability of Gluconobacter oxydans to produce 2-KLG. The supernate of GB82 sampled at different cultivation times all had much more activity to spur Gluconobacter oxydans to yield 2-KLG than that of the original B. megaterium, which might be due to the genetic changes in the active components caused by ion implantation. Furthermore, the active substances of GB82's supernate would lose a part of its activity in extreme environments, which is typical of some proteins.
基金Supported by Shenzhen High-level Hospital Construction Fund.
文摘BACKGROUND Patients harboring gene mutations like KRAS,NRAS,and BRAF demonstrate highly variable responses to chemotherapy,posing challenges for treatment optimization.Multiparametric magnetic resonance imaging(MRI),with its noninvasive capability to assess tumor characteristics in detail,has shown promise in evaluating treatment response and predicting therapeutic outcomes.This technology holds potential for guiding personalized treatment strategies tailored to individual patient profiles,enhancing the precision and effectiveness of colorectal cancer care.AIM To create a multiparametric MRI-based predictive model for assessing chemotherapy efficacy in colorectal cancer patients with gene mutations.METHODS This retrospective study was conducted in a tertiary hospital,analyzing 157 colorectal cancer patients with gene mutations treated between August 2022 and December 2023.Based on chemotherapy outcomes,the patients were categorized into favorable(n=60)and unfavorable(n=50)response groups.Univariate and multivariate logistic regression analyses were performed to identify independent predictors of chemotherapy efficacy.A predictive nomogram was constructed using significant variables,and its performance was assessed using the area under the receiver operating characteristic curve(AUC)in both training and validation sets.RESULTS Univariate analysis identified that tumor differentiation,T2 signal intensity ratio,tumor-to-anal margin distance,and MRI-detected lymph node metastasis as significantly associated with chemotherapy response(P<0.05).Multivariate Logistics regression confirmed these four parameters as independent predictors.The predictive model demonstrated strong discrimination,with an AUC of 0.938(sensitivity:86%;specificity:92%)in the training set,and 0.942(sensitivity:100%;specificity:83%)in the validation set.CONCLUSION We established and validated a multiparametric MRI-based model for predicting chemotherapy response in colorectal cancer patients with gene mutations.This model holds promise for guiding individualized treatment strategies.
基金supported by the Fundamental Research Funds for the Central Universities of China(2572022DQ03)the National Natural Science Foundation of China(32170517)+2 种基金the Guangdong Provincial Key Laboratory of Genome Read and Write(2017B030301011)the Start-up Scientific Foundation of Northeast Forestry University(60201524043)supported by China National GeneBank(CNGB).
文摘Inbreeding increases genome homozygosity within populations,which can exacerbate inbreeding depression by exposing homozygous deleterious alleles that are responsible for declines in fitness traits.In small populations,genetic purging that occurs under the pressure of natural selection acts as an opposing force,contributing to a reduction of deleterious alleles.Both inbreeding and genetic purging are paramount in the field of conservation genomics.The Amur tiger(Panthera tigris altaica)lives in small populations in the forests of Northeast Asia and is among the most endangered animals on the planet.Using genome-wide assessment and comparison,we reveal substantially higher and more extensive inbreeding in wild Amur tigers(F_(ROH)=0.50)than in captive individuals(F_(ROH)=0.24).However,a relatively reduced number of lossof-function mutations in wild Amur tigers is observed compared to captive individuals,indicating genetic purging of inbreeding load with relatively large-effect alleles.The higher ratio of homozygous mutation load and number of fixed damaging alleles in the wild population indicates a less-efficient genetic purging,with purifying selection also contributing to this process.These findings provide valuable insights for the future conservation of Amur tigers.
基金supported by the National Key R&D Program of China(No.2021YFB3400900)the National Natural Science Foundation of China(Nos.52175373,52205435)+1 种基金Natural Science Foundation of Hunan Province,China(No.2022JJ40621)the Innovation Fund of National Commercial Aircraft Manufacturing Engineering Technology Center,China(No.COMACSFGS-2022-1875)。
文摘A new unified constitutive model was developed to predict the two-stage creep-aging(TSCA)behavior of Al-Zn-Mg-Cu alloys.The particular bimodal precipitation feature was analyzed and modeled by considering the primary micro-variables evolution at different temperatures and their interaction.The dislocation density was incorporated into the model to capture the effect of creep deformation on precipitation.Quantitative transmission electron microscopy and experimental data obtained from a previous study were used to calibrate the model.Subsequently,the developed constitutive model was implemented in the finite element(FE)software ABAQUS via the user subroutines for TSCA process simulation and the springback prediction of an integral panel.A TSCA test was performed.The result shows that the maximum radius deviation between the formed plate and the simulation results is less than 0.4 mm,thus validating the effectiveness of the developed constitutive model and FE model.
文摘BACKGROUND Thrombophilia contributes to a significant increased risk of venous thromboembolism and can be either inherited or acquired.Hereditary thrombophilia may arise from various gene mutations,some of which have not even been adequately reported or poorly understood.Previous studies reported a rare and novel missense mutation in the prothrombin gene(p.Arg596Gln),known as prothrombin Belgrade.The mechanisms and therapeutic strategies associated with prothrombin Belgrade mutation have not been fully elucidated.CASE SUMMARY We present the case of a 26-year-old woman with recurrent systemic thrombosis induced by prothrombin Belgrade mutation.The patient suffered from cerebral venous sinus thrombosis that rapidly progressed to systemic thrombosis,alongside a family history of cerebral thrombosis,and no traditional risk factors or abnormal coagulation function.Whole-genome sequencing detected a novel and rare heterozygous prothrombin missense mutation,c.1787G>T(p.Arg596Gln),which was responsible for the major etiology of the systemic thrombosis.CONCLUSION This case strengthens our understanding about hereditary basis of thrombophilia and provokes considerations for therapeutic options on prothrombin Belgrade mutation.
基金Supported by the Medical Education Collaborative Innovation Fund of Jiangsu University,No.JDY2022015。
文摘BACKGROUND Through deeper understanding of targetable driver mutations in non-small-cell lung cancer(NSCLC)over the past years,some patients with driver mutations have benefited from the targeted molecular therapies.Although the anaplastic lymphoma kinase and BRAF mutations are not frequent subtypes in NSCLC,the availability of several targeted-drugs has been confirmed through a series of clinical trials.But little is clear about the proper strategy in rare BRAF G469A mutation,not to mention co-exhibition of anaplastic lymphoma kinase and BRAF G469A mutations,which is extremely rare in NSCLC.CASE SUMMARY We present a patient to stage IVA lung adenocarcinoma with coexisting echinoderm microtubule associated protein like-4 rearrangement and BRAF G469A mutation.She received several targeted drugs with unintended resistance and suffered from unbearable adverse events.CONCLUSION Due to the rarity of co-mutations,the case not only enriches the limited literature on NSCLC harbouring BRAF G469A and echinoderm microtubule associated protein like-4 mutations,but also suggests the efficacy and safety of specific multiple-drug therapy in such patients.
基金supported by the National Natural Science Foundation(82271057)the Natural Science Foundation of Hunan Province(2023JJ30818),China。
文摘Objective:Keratoconus(KC)is a progressive corneal ectasia disorder,arising from a myriad of causes including genetic predispositions,environmental factors,biomechanical influences,and inflammatory reactions.This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population.Methods:Twenty-five patients with primary KC as well as 50 unrelated population matched healthy controls,were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population.Sanger sequencing and whole-exome sequencing(WES)were used to analyze mutations in the zinc finger protein 469(ZNF469)gene.Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis.Results:Five novel heterozygous missense variants were identified in KC patients.Among them,2 compound heterozygous variants,c.8986G>C(p.E2996Q)with c.11765A>C(p.D3922A),and c.4423C>G(p.L1475V)with c.10633G>A(p.G3545R),were determined to be possible pathogenic factors for KC.Conclusion:Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population.These mutation sites may provide valuable information for future genetic screening of KC patients and their families.
基金Supported by Natural Science Foundation of Shanghai,No.17ZR1431400National Key R and D Program of China,No.2017YFA0103902.
文摘Sotos syndrome is characterized by overgrowth features and is caused by alterations in the nuclear receptor binding SET domain protein 1 gene.Attentiondeficit/hyperactivity disorder(ADHD)is considered a neurodevelopment and psychiatric disorder in childhood.Genetic characteristics and clinical presentation could play an important role in the diagnosis of Sotos syndrome and ADHD.Magnetic resonance imaging(MRI)has been used to assess medical images in Sotos syndrome and ADHD.The images process is considered to display in MRI while wavelet fusion has been used to integrate distinct images for achieving more complete information in single image in this editorial.In the future,genetic mechanisms and artificial intelligence related to medical images could be used in the clinical diagnosis of Sotos syndrome and ADHD.
文摘BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qualitatively various protein activities,which may be reflected in their differential association with tumor characteristics.AIM To examine the association between these mutations and colorectal cancer(CRC)progression stages.METHODS A retrospective analysis was conducted on 799 patients with CRC,whose tumor samples were examined for mutations in the hot-spots of the KRAS,NRAS,and BRAF genes at the University of Texas Medical Branch,spanning from January 2016 to July 2023.Statistical analyses were performed to assess the association of spe-cific nucleotide changes with tumor,nodes,and metastasis stages.RESULTS KRAS mutations were found in 39.5%of cases,NRAS mutations in 4.4%,and BRAF mutations in 6.0%.The KRAS p.Gly12Val and p.Gly13Asp mutations were positively associated with pathological stage 4 tumors.Additionally,the KRAS p.Gly12Asp and p.Gly12Val mutations were linked to an increased risk of distant metastasis.Meanwhile,the BRAF Val600Glu mutation was associated with a higher likelihood of lymph node involvement.CONCLUSION Our findings support the potential prognostic utility of specific KRAS(p.Gly12Val,p.Gly12Asp,and p.Gly13Asp)and BRAF p.Val600Glu mutations in CRC.These results are preliminary and require validation through larger,multi-center studies before they can be considered reliable in clinical practice.
基金Supported by Jilin Province Science and Technology Development Project,No.20220203018SF。
文摘BACKGROUND Only a few cases of diabetes mellitus with concurrent mutations in the mitochondrial MT-TL1 and CEL genes have been reported worldwide.Racial differences may influence mutation frequency,the presentation of symptoms,and disease progression.This case report describes the clinical features,potential genetic mechanisms,and diagnostic complexity of young-onset diabetes mellitus with concurrent m.3243A>G mutation in MT-TL1 and c.1336G>A mutation in CEL.The objective is to inform precise typing,genetic counseling,and personalized treatment of monogenic diabetes mellitus,while expanding the evidence base on rare forms of diabetes mellitus.CASE SUMMARY A 30-year-old man,diagnosed with diabetic ketoacidosis six years earlier,presented with poor response to insulin therapy(glycated hemoglobin,15.35%),marked wasting(body mass index:15.06 kg/m2),sensorineural deafness,diabetic retinopathy,and peripheral neuropathy.Whole-exome sequencing revealed concurrent mutations:Mitochondrial MT-TL1 m.3243A>G(heteroplasmy 41.76%)and CEL c.1336G>A.Family investigation identified his mother,who also had diabetes,as a carrier of the CEL mutation,and his sister as harboring both mutations without diabetes.CONCLUSION This case highlights the genetic heterogeneity of monogenic diabetes and expands the known mutational spectrum.Comprehensive genetic testing is recommended to enhance diagnostic accuracy in cases of suspected monogenic diabetes.
基金supported by National Natural Science Foundation of China(Grant No.62266028,62266027,U21B2027,and U24A20334)Major Science and Technology Programs in Yunnan Province(Grant No.202302AD080003,202402AG050007,and 202303AP140008)+1 种基金Yunnan Province Basic Research Program(Grant No.202301AS070047,202301AT070471,and 202401BC070021)Kunming University of Science and Technology's"Double First-rate"construction joint project(Grant No.202201BE070001-021).
文摘Lexical analysis is a fundamental task in natural language processing,which involves several subtasks,such as word segmentation(WS),part-of-speech(POS)tagging,and named entity recognition(NER).Recent works have shown that taking advantage of relatedness between these subtasks can be beneficial.This paper proposes a unified neural framework to address these subtasks simultaneously.Apart from the sequence tagging paradigm,the proposed method tackles the multitask lexical analysis via two-stage sequence span classification.Firstly,the model detects the word and named entity boundaries by multilabel classification over character spans in a sentence.Then,the authors assign POS labels and entity labels for words and named entities by multi-class classification,respectively.Furthermore,a Gated Task Transformation(GTT)is proposed to encourage the model to share valuable features between tasks.The performance of the proposed model was evaluated on Chinese and Thai public datasets,demonstrating state-of-the-art results.
基金Project(52274348)supported by the National Natural Science Foundation of ChinaProject(2022JH1/10400024)supported by the Major Projects for the“Revealed Top”Science and Technology of Liaoning Province,China。
文摘Applying bio-oxidation waste solution(BOS)to chemical-biological two-stage oxidation process can significantly improve the bio-oxidation efficiency of arsenopyrite.This study aims to clarify the enhanced oxidation mechanism of arsenopyrite by evaluating the effects of physical and chemical changes of arsenopyrite in BOS chemical oxidation stage on mineral dissolution kinetics,as well as microbial growth activity and community structure composition in bio-oxidation stage.The results showed that the chemical oxidation contributed to destroying the physical and chemical structure of arsenopyrite surface and reducing the particle size,and led to the formation of nitrogenous substances on mineral surface.These chemical oxidation behaviors effectively promoted Fe^(3+)cycling in the bio-oxidation system and weakened the inhibitory effect of the sulfur film on ionic diffusion,thereby enhancing the dissolution kinetics of the arsenopyrite.Therefore,the bio-oxidation efficiency of arsenopyrite was significantly increased in the two-stage oxidation process.After 18 d,the two-stage oxidation process achieved total extraction rates of(88.8±2.0)%,(86.7±1.3)%,and(74.7±3.0)%for As,Fe,and S elements,respectively.These values represented a significant increase of(50.8±3.4)%,(47.1±2.7)%,and(46.0±0.7)%,respectively,compared to the one-stage bio-oxidation process.
文摘Objective:To investigate the clinical and molecular genetic characteristics of Chinese adolescents with maturity-onset diabetes of the young type 2(MODY 2)and the safety and efficacy of recombinant human growth hormone(r-hGH).Methods:The clinical features and laboratory data of a family with MODY 2 combined with partial growth hormone deficiency(pGHD),diagnosed at the Fourth Clinical Medical College of Xinjiang Medical University,were analyzed.DNA was extracted from peripheral blood using the column method,and Sanger sequencing was conducted to analyze the glucokinase(GCK),hepatocyte nuclear factor 1α(HNF1α),and hepatocyte nuclear factor 4α(HNF4α)in the proband and relevant family members.Results:A heterozygous mutation in GCK(Reference sequence:NM_000162,location:Exon 10)c.1340G>A(p.R447Q)was detected in three family members(the proband,the proband’s younger brother,and their mother).The proband also had pGHD.Conclusion:GCK mutations causing MODY 2 exist in the Chinese population,and the combined treatment with r-hGH is safe and effective.
基金supported by the Natural Science Foundation of Fujian Province,No.2020J02027the National Natural Science Foundation of China,No.31970461the Foundation of NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate,Fujian Maternity and Child Health Hospital,No.2022-NHP-05(all to WC).
文摘Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.
基金supported by grants from the National Natural Science Foundation of China(32170238,32400191)Guangdong Basic and Applied Basic Research Foundation(2023A1515111029)+2 种基金the Science,Technology and Innovation Commission of Shenzhen Municipality(RCYX20200714114538196)the Chinese Academy of Agricultural Sciences Elite Youth Program(grant 110243160001007)the Guangdong Pearl River Talent Program(2021QN02N792)。
文摘Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(SSB1 and SSB2).However,the functional divergence of these two SSB copies in plants remains largely unknown,and detailed studies regarding their roles in the replication and recombination of organellar genomes are still incomplete.In this study,phylogenetic,gene structure and protein motif analyses all suggested that SSB1 and SSB2 probably diverged during the early evolution of seed plants.Based on accurate long-read sequencing results,ssb1 and ssb2 mutants had decreased copy numbers for both mitochondrial DNA(mtDNA)and plastid DNA(ptDNA),accompanied by a slight increase in structural rearrangements mediated by intermediate-sized repeats in mt genome and small-scale variants in both genomes.Our findings provide an important foundation for further investigating the effects of DNA dosage in the regulation of mutation frequencies in plant organellar genomes.
基金the National Natural Science Foundation of China[Grant No.52270183].
文摘Exploring the factors driving the decoupling of China’s sulfur dioxide(SO_(2))emissions from economic growth(DEI)is crucial for achieving sustainable development.By analyzing the decoupling indicators and driving factors at both the generation and treatment stages of SO_(2),more effective targeted mitigation strategies can be developed.We employ the Tapio decoupling model and propose a two-stage method to examine the decoupling issues related to SO_(2).Our findings indicate that:①DEI shows a steady and significant improvement,with SO_(2)emission intensity identified as the primary driver.②for the decoupling of economic growth and SO_(2)generation,energy scale serves as the largest stimulator,while the effect of energy intensity changes from negative to positive,and pollution intensity is first positive and then negative.③For the decoupling of SO_(2)generation and SO_(2)removal,treatment efficiency leads as the largest promoter,followed by treatment intensity.Based on these results,this study recommends that China focuses more on enhancing clean energy utilization and the effectiveness of treatment processes.
文摘BACKGROUND Two-stage revision is the most common treatment for chronic periprosthetic joint infection of the hip,involving a resection arthroplasty with or without placement of an antibiotic-loaded spacer,followed by antibiotic therapy before reimplantation.AIM To compare the outcomes and complications of two consecutive treatment protocols for two-stage revision arthroplasty of the infected hip:One using Girdlestone with an antibiotic holiday,the other using custom-made articulating spacers(CUMARS)without an antibiotic holiday.METHODS In this retrospective study,two consecutive cohorts were compared.Group A(2017-2020)underwent two-stage revision with a Girdlestone and an antibiotic holiday before reimplantation,while Group B(2020-2023)received CUMARS whenever possible,and no antibiotic holiday,or a Girdlestone if indicated.The primary outcome was successful infection eradication after one year.Secondary outcomes included surgical duration,length of hospital stay,weight-bearing allowance,discharge destination,and complications.RESULTS A total of 98 patients were included:39 patients in Group A and 59 patients in Group B.Successful infection eradication after one year was achieved in 69%of Group A and 83%of Group B(P=0.164).Patients in Group B were more frequently allowed to bear weight(64%vs 18%,P<0.001),had a shorter in-hospital stay(9 vs 16 days,P<0.001),and were more often discharged home after the first surgery(48%vs 24%,P=0.048).No significant differences were found in(mechanical)complications.CONCLUSION A protocol including CUMARS is a safe and effective treatment,offering faster recovery,shorter length of hospital stay,and enabling more patients to return home during the interval.This reduces strain on patients and the healthcare system,potentially saving costs,without compromising infection control or increasing(mechanical)complications.
