AIM: To investigate whether the changes of gap junction gene connexin messenger RNA in the noncancerous liver tissue of patients with hepatocellular carcinoma (HCC) could play a significant role in its postresection r...AIM: To investigate whether the changes of gap junction gene connexin messenger RNA in the noncancerous liver tissue of patients with hepatocellular carcinoma (HCC) could play a significant role in its postresection recurrence.METHODS: Seventy-nine consecutive patients having undergone curative resection for HCC entered this study.Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, connexin (Cx) 26, connexin (Cx)32 and connexin (Cx) 43 mRNAs were determined prospectively in noncancerous liver tissues from these 79 patients and in the liver tissues from 15 controls. The correlations between connexin mRNA expression and the clinicopathological variables and outcomes (tumor recurrence and recurrence related mortality) were studied.RESULTS: Compared with liver tissues of control patients,the expression of Cx 32 mRNA in noncancerous liver tissues was significantly lower (mean: 0.715 vscontrol 1.225,P＜0.01), whereas the decreased Cx 26 mRNA (mean:0.700 vs of control 1.205,P＞0.05) and increased Cx 43 mRNA (mean: 0.241 vscontrol 0.100, P＞0.05) had no statistical significance. We defined the value of Cx 32 mRNA or Cx 26mRNA below 0.800 as a lower value. By multivariate analysis for noncancerous livers, a lower value of Cx 32 mRNA correlated significantly with a risk of HCC recurrence and recurrence-related mortality. The lower value of Cx 26 mRNA did not correlate with recurrence and mortality. The increased value of Cx43 mRNA also did not correlate with postoperative recurrence and recurrence-related mortality. By multivariate analysis, other significant predictors of HCC recurrence included vascular permeation, cellular dedifferentiation, and less encaps-ulation. The other significant parameter of recurrence related mortality was vascular permeation.CONCLUSION: The decreased expression of Cx 32 mRNA in noncancerous liver tissues plays a significant role in the prediction of postoperative recurrence of HCC.展开更多
We show that the nonlinear stage of the dual-wavelength pumped modulation instability(MI)in nonlinear Schrödinger equation(NLSE)can be effectively analyzed by mode truncation methods.The resulting complicated het...We show that the nonlinear stage of the dual-wavelength pumped modulation instability(MI)in nonlinear Schrödinger equation(NLSE)can be effectively analyzed by mode truncation methods.The resulting complicated heteroclinic structure of instability unveils all possible dynamic trajectories of nonlinear waves.Significantly,the latticed-Fermi-Pasta-Ulam recurrences on the modulated-wave background in NLSE are also investigated and their dynamic trajectories run along the Hamiltonian contours of the heteroclinic structure.It is demonstrated that there has much richer dynamic behavior,in contrast to the nonlinear waves reported before.This novel nonlinear wave promises to inject new vitality into the study of MI.展开更多
Let A∈N,B∈Z with gcd(A,B)=1,B{-1,0,1}. For the binary recurrence (Lucas sequence) of the form u 0=0, u 1=1, u n+2 =Au n+1 +Bu n, let N 1(A,B,k) be the number of the terms n of |u n|=k, where k∈N. In this paper, usi...Let A∈N,B∈Z with gcd(A,B)=1,B{-1,0,1}. For the binary recurrence (Lucas sequence) of the form u 0=0, u 1=1, u n+2 =Au n+1 +Bu n, let N 1(A,B,k) be the number of the terms n of |u n|=k, where k∈N. In this paper, using a new result of Bilu, Hanrot and Voutier on primitive divisors, we proved that N 1(A,B,k)≤1 except N 1(1,-2,1)=5[n=1,2,3,5,13], N 1(1,-3,1)=3, N 1(1,-5,1)=3,N 1(1,B,1)=2(B{-2,-3,-5}), N 1(12,-55,1)=2, N 1(12,-377,1)=2, N 1(A,B,1)=2(A 2+B=±1, A>1), N 1(1,-2,3)=2, N 1(A,B,A)=2(A 2+2B=±1,A>1. For Lehmer sequence, we got a similar result. In addition, we also obtained some applications of the above results to some Diophantime equations.展开更多
Early recurrence of atrial arrhythmias(ERAA) after ablation is common and strongly predicts late recurrences and ablation failure. However, since arrhythmia may eventually resolve in up to half of patients with ERAA, ...Early recurrence of atrial arrhythmias(ERAA) after ablation is common and strongly predicts late recurrences and ablation failure. However, since arrhythmia may eventually resolve in up to half of patients with ERAA, guidelines do not recommend immediate reintervention for ERAA episodes occurring during a 3-mo postablation blanking period. Certain clinical demographic, electrophysiologic, procedural, and ERAA-related characteristics may predict a higher likelihood of longterm ablation failure. In this review, we aim to discuss potential mechanisms of ERAA, and to summarize the clinical significance, prognostic implications, and treatment options for ERAA.展开更多
AIM： To evaluate a series of patients with hepatocellular carcinoma （HCC） treated with several different protocols and devices. METHODS： We treated 138 patients [chronic hepatitis/ liver cirrhosis （Child-Pugh A/...AIM： To evaluate a series of patients with hepatocellular carcinoma （HCC） treated with several different protocols and devices. METHODS： We treated 138 patients [chronic hepatitis/ liver cirrhosis （Child-Pugh A/B/C）, 3/135 （107/25/3）] with two different devices and protocols： cool-tip needle [initial ablation at 60 W （standard method） （n = 37） or at 40 W （modified method） （n = 28）] or; ablation with a LeVeen needle using a standard single-step, full expansion （single-step） method （n = 39） or a multi-step, incremental expansion （multi-step） method. RESULTS： Eleven patients experienced rapid and scattered recurrences 1 to 7 mo after the ablation. Nine patients were treated by the cool-tip original protocol （60 W） （9/37 = 24%） and the other two by the LeVeen single-step method （2/39 = 5%）. The location of the recurrence was surrounding and limited to the site of ablation segment in three cases, and spread over one Iobule or both Iobules in the other eight cases. There was no recurrence in the patients treated with the modified cool-tip modified method （40 W） or the LeVeen multi-step method. CONCLUSION： There is a risk of rapid and scattered recurrence after RFA, especially when the standard cool- tip procedure is used. Because such recurrence would worsen the prognosis, we recommend that modified protocols for the cool-tip and LeVeen needle methods should be used in clinical practice.展开更多
Objective: Most recurrent intrahepatic cholangiocarcinoma (RICC) lost the opportunity of radical resection while most nonsurgical management failed to prolong patients’ survival. The efficacy and safety of radiofrequ...Objective: Most recurrent intrahepatic cholangiocarcinoma (RICC) lost the opportunity of radical resection while most nonsurgical management failed to prolong patients’ survival. The efficacy and safety of radiofrequency ablation (RFA) as a local treatment for recurrent hepatocellular carcinoma have been confirmed by many clinical studies. The purpose of this study was to evaluate the efficacy, long-term survival and complications of RFA for RICC. Methods: A total of 12 patients with 19 RICCs after radical resection were included in this study. The tumors were 1.9–6.8 cm at the maximum diameter (median, 3.2±1.6 cm). All patients were treated with ultrasound guided RFA. There were two RFA approaches including percutaneous and open. Results: A total of 18 RFA treatment sessions were performed. Ablation was successful (evaluated by 1-month CT after the initial RFA procedure) in 18 (94.7%) of 19 tumors. By a median follow-up period of 29.9 months after RFA, 5 patients received repeated RFA because of intrahepatic lesion recurrence. The median local recurrence-free survival period and median event-free survival period after RFA were 21.0 months and 13.0 months, respectively. The median overall survival was 30 months, and the 1- and 3-year survival rates were 87.5% and 37.5%, respectively. The complication rate was 5.6% (1/18 sessions). The only one major complication was pleural effusion requiring thoracentesis. Conclusion: This study showed RFA may effectively and safely manage RICC with 3-year survival of 37.5%. It provides a treatment option for these RICC patients who lost chance for surgery.展开更多
AIM:To analyze the anatomical and functional outcomes in the inferior recurrences of rhegmatogenous retinal detachment(RRD)depending on the surgical approach.METHODS:Eighty-one eyes of 81 patients(47 males and 34 fema...AIM:To analyze the anatomical and functional outcomes in the inferior recurrences of rhegmatogenous retinal detachment(RRD)depending on the surgical approach.METHODS:Eighty-one eyes of 81 patients(47 males and 34 females with a mean age of 54.8±14.1y)who demonstrated at least one inferior recurrence of RRD were included in this retrospective study.All patients were categorized as having received either circular scleral buckling(SB),pars plana vitrectomy(PPV),a combination of SB and PPV(SB+PPV),PPV with retinotomy(PPV+RT),or PPV+RT and short-term postoperative perfluorocarbon liquid tamponade(PPV+RT+pPFCL).All cases were followed up until successful retinal reattachment or third recurrence.The primary outcome measures were the achievement of the surgical goal without recurrence of RRD and bestcorrected visual acuity(BCVA).RESULTS:After the treatment of the first recurrence,the recurrence rate in the PPV+SB group was statistically significantly lower than that of the PPV(P=0.0012),PPV+RT(P=0.028),or PPV+RT+pPFCL(P=0.047)group.There was no statistically significant difference between PPV+SB,PPV+RT,and PPV+RT+pPFCL groups in the recurrence rate after treatment of the second recurrence(42 eyes).However,there was a statistically significant(P=0.016)trend towards a decrease of recurrence rate after PPV+RT+pPFCL.There was no statistically significant improvement of BCVA in either study group(P>0.05)after both first and second recurrence surgery.The mean time follow-up was 109.0±91.0d before the first recurrence and 210.0±186.6d between previous surgery at second recurrence.CONCLUSION:Patients with first inferior recurrence of RRD may benefit from SB as an adjunct to PPV.RT and short-term pPFCL tamponade in the second recurrence may allow better anatomical outcomes,however,without functional improvement.展开更多
AIM: To investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence.METHODS: From the pathology department database, we retrospectively retrieved the data of all the ...AIM: To investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence.METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohn’s disease (CD) in our center (1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy (median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy.RESULTS: From 205 patients who underwent surgery, 161 patients (follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype (B3) were postoperative risk factors. Previous perianal abscess/fistula (other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management (n = 49/161) prevented clinical (HR = 0.4, 95%CI: 0.25-0.66, P < 0.001) and surgical postoperative recurrence (HR = 0.30, 95%CI: 0.13-0.70, P = 0.006).CONCLUSION: Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation.展开更多
Background: Bacterial vaginosis (BV) is the most common urogenital disease in women, affecting about 19% - 24% of them in reproductive ages annually and after treatment, a single recurrence or more may occur in up to ...Background: Bacterial vaginosis (BV) is the most common urogenital disease in women, affecting about 19% - 24% of them in reproductive ages annually and after treatment, a single recurrence or more may occur in up to 58% of women within 12 months. Objective: The aim was to evaluate the effectiveness of a new orally administered food supplement, containing different probiotic strains, on women of childbearing age after the antibiotic treatment when compared with no probiotic intake. Methods: A prospective study was undertaken on 62 patients with BV. All patients were cured with metronidazole vaginal formulations (5 g of 0.75% gel once daily for 5 days or 500 mg ovules once daily for 7 days), then after was offered the option of using a new an orally administered food supplement containing: Lactobacillus plantarum PBS067, Lactobacillus rhamnosus LRH020 and Bifidobacterium animalis lactis BL050, with a total viability of 3 × 109 CFU/capsule (Intimique®Femme). Among these women, 50 accepted to use the new orally food supplement, while 25 patients decided to use only metronidazole (control group). Results: The recurrence rate of BV after treatment with Intimique®Femme was about 16%, compared to 40% in the control group. The incidence of abnormal vaginal microbiota decreased in both groups, but it was significantly higher in the Intimique®Femme group at the end of treatment. Conclusion: This study showed that, in case of BV diagnosis, the complementary treatment of a strain-specific probiotic complex after antibiotics prophylaxis, is mandatory to reduce potential recurrences and cyclic use of further antibiotics.展开更多
We report a case of myxoma with multiple recurrences in both the atrium and ventricle in a 26-year-old woman five years after the surgical removal of left atrial myxoma, Her 52-year-old mother had a similar medical hi...We report a case of myxoma with multiple recurrences in both the atrium and ventricle in a 26-year-old woman five years after the surgical removal of left atrial myxoma, Her 52-year-old mother had a similar medical history. To our knowledge, this was the first familial case who suffered multifocal cardiac myxoma recurrences without any sign of the myxoma complex. Based on our understanding of the mechanism of recurrence, the approaches to prevent the recurrence, and markers to predict recurrence, we propose that multifocal recurrences, as reported herein, may result from a combination of familial predisposition and multifocal onset. The hi-atrial surgical approach and transesophageal echocardiography are preferred for patients with recurrent cardiac myxomas, especially for those with multiple recurrences and familial myxoma. Immunological and genetic screenings may help to identify family members at risk for developing this disease.展开更多
Background: Sentinel node biopsy (SNB) was introduced at Ullevaal University Hospital in 2000. This article presents results from the first ten years use of the method. Material and Methods: A prospective registration...Background: Sentinel node biopsy (SNB) was introduced at Ullevaal University Hospital in 2000. This article presents results from the first ten years use of the method. Material and Methods: A prospective registration of 2762 patients was made from 2000 through 2009. Results: The median follow-up time was 51 months. The overall detection rate was 93%. 36% of the patients with positive SNs had non-sentinel metastases. These were significantly associated with a macrometastatic SN and a primary tumour>20 mm. 18% of patients with sentinel metastasis≤2 mm had non-sentinel metastases. 14 patients with negative SN (0.7%) developed axillary recurrence. 32% with a preoperative diagnosis of ductal carcinoma in situ (DCIS) were upstaged to infiltrating carcinoma on final histology. None of the patients with pure DCIS had positive SNs. Conclusion: Few late events (0.7%) in SN negative axillas demonstrate the safety of the technique.展开更多
Recurrent pregnancy loss(RPL)affects 2%-5%of couples attempting to conceive.It is a highly heterogenous condition attributed to several factors including endocrine dysfunction,auto immune disorders,thrombophilia,genet...Recurrent pregnancy loss(RPL)affects 2%-5%of couples attempting to conceive.It is a highly heterogenous condition attributed to several factors including endocrine dysfunction,auto immune disorders,thrombophilia,genetic abnormalities,infectious diseases,uterine anomalies,sperm DNA fragmentation,and epigenetics.Among genetic causes,chromosomal abnormalities are the most frequent etiological factor of early miscarriage,accounting for 50%–60%of first trimester abortions.Numerical or structural chromosomal changes may result in spontaneous miscarriages.These anomalies arise as a result of chromosomal translocation,non-disjunction,or mutations[1].Transmission of parental chromosomal abnormalities may be one of the chances for a recurrence of miscarriage in the first trimester of pregnancy,albeit the cause is unknown[2,3].展开更多
Objectives:Tumor recurrence is a major determinant of poor prognosis in hepatocellular carcinoma(HCC),yet its cellular and molecular basis remains incompletely understood.This study aimed to identify recurrenceassocia...Objectives:Tumor recurrence is a major determinant of poor prognosis in hepatocellular carcinoma(HCC),yet its cellular and molecular basis remains incompletely understood.This study aimed to identify recurrenceassociated genes at single-cell resolution and to develop a prognostic model for predicting survival outcomes and immunotherapy responsiveness in HCC.Methods:Single-cell RNA sequencing data from 12 primary and 6 recurrent HCC samples were integrated and analyzed to identify genes characteristic of recurrence.After quality control,principal component analysis,and t-SNE-based clustering were used to identify highly variable genes for cell clustering and annotation.Based on macrophage characteristic genes,a recurrence-related risk score was constructed using a LASSOCox regression model,and a nomogram integrating clinical variables was developed.Prognostic performance was assessed using Kaplan-Meier analysis and time-dependent ROC curves.Immune infiltration profiling was performed to compare immune characteristics between risk groups defined by the prognostic model.Multivariate Cox regression was applied to identify independent prognostic biomarkers,which were subsequently validated by cell function experiments.Results:The risk model effectively stratified patients into high-and low-risk groups with distinct survival outcomes,demonstrating high predictive accuracy for 1-,3-,and 5-year survival.High-risk patients showed altered immune profiles and a reduced predicted response to immunotherapy.GRID2,RNF186,and SLC4A10 were identified as independent prognostic genes,with RNF186 promoting HCC cell proliferation in a SESN2-dependent manner.Conclusion:This prognostic model provides new insights into precision medicine and immunotherapy for HCC,highlighting the potential clinical significance of RNF186 as a therapeutic target.展开更多
AIM:To evaluate the efficacy and safety of decellularized conjunctival stroma(DCS)as a novel biomaterial by comparing its grafting outcomes with amniotic membrane(AM)when used for conjunctival reconstruction after pri...AIM:To evaluate the efficacy and safety of decellularized conjunctival stroma(DCS)as a novel biomaterial by comparing its grafting outcomes with amniotic membrane(AM)when used for conjunctival reconstruction after primary pterygium excision.METHODS:This randomized,parallel-controlled study with allocation concealment enrolled 40 patients with primary pterygium.Participants were randomly assigned to two groups using the sealed envelope method:the DCS group(n=20)and the AM group(n=18),receiving DCS and AM grafts respectively.Slit-lamp photography of the operative eyes was performed preoperatively and at 1,3,5,7,10,30,90,and 180d postoperatively.Best-corrected visual acuity(BCVA)and symptom scores were recorded simultaneously.In vivo confocal microscopy was conducted at 3 and 6mo postoperatively.RESULTS:All participants exhibited improved postoperative symptoms.The mean age was 60±9y(male/female ratio:6/14)in the DCS group and 56±12y(male/female ratio:7/11)in the AM group.The average epithelial healing time was 9.89±3.54d in the DCS group and 8.17±1.34d in the AM group(P=0.084).One recurrence case was observed in each group.Postoperative graft hemorrhage was significantly more severe in the DCS group than in the AM group only at 30d postoperatively(P=0.011).In vivo confocal microscopy revealed conjunctival epithelial cell growth in both groups at 90d postoperatively,while clear corneo-conjunctival cell boundaries were observed until 180d postoperatively.CONCLUSION:DCS used in primary pterygium surgery has a safety profile comparable to AM.It promotes rapid postoperative conjunctival healing,achieves a relatively low pterygium recurrence rate,and yields outcomes similar to AM.DCS provides a novel biomaterial option for conjunctival reconstruction after pterygium excision and the treatment of other conjunctival injuries.展开更多
The accurate state of health(SOH)estimation in lithium-ion batteries represents a critical technological challenge with profound implications for electric vehicle performance and user experience.Precise SOH assessment...The accurate state of health(SOH)estimation in lithium-ion batteries represents a critical technological challenge with profound implications for electric vehicle performance and user experience.Precise SOH assessment not only enables reliable mileage prediction but also ensures operational safety.However,the complex and non-linear capacity fading process during battery cycling poses a challenge to obtaining accurate SOH.To address this issue,this study proposes an effective health factor derived from the local voltage range during the battery charging phase.First,the battery charging phase is divided evenly with reference to voltage intervals,and an importance analysis is conducted on each voltage interval.From these,the voltage interval with the strongest correlation to State of Health(SOH)is extracted as the feature interval.Then,a data-driven framework integrating variational mode decomposition(VMD)with gated recurrent unit(GRU)neural networks enables comprehensive multi-scale temporal feature analysis for enhanced SOH estimation.The methodology begins with rigorous feature engineering to identify and extract optimal health indicators demonstrating superior correlation.Subsequently,the VMD algorithm performs sophisticated signal processing to decompose both the measured capacity and derived health indicators into their constituent intrinsic mode functions and residual components.Finally,a GRU-based neural network is implemented to establish a robust SOH estimation model.Experimental validation using cycling data from different datasets shows that the root mean square error of the estimation results is consistently below 3%,demonstrating the good accuracy and generalisation of the proposed method,using only local data from the charging phase.展开更多
This study examines a 1.32 m thick sediment sequence from the Cunge sag pond in the Litang Basin,eastern Tibetan Plateau,to assess the seismicity of the Litang fault during the Holocene.High-resolution geochemical,gra...This study examines a 1.32 m thick sediment sequence from the Cunge sag pond in the Litang Basin,eastern Tibetan Plateau,to assess the seismicity of the Litang fault during the Holocene.High-resolution geochemical,grain size,magnetic susceptibility,and total organic carbon indicators are employed to obtain a continuous record of changes in elemental,physical,and biological properties within the profile to identify seismic events.The seismic event layer generally comprises two sedimentary rhythms:a lower coarse sand layer and an upper fine silt-clay layer.These layers represent rapid deposition associated with fault activity(Earthquake A)and slower deposition during calm periods or earthquake recurrence intervals(Seismic interval A).Through six^(14)C dating,five seismic events have been identified in the Cunge sag pond section:E1(before 3955 a B.P.),E2(3713-3703 a B.P.),E3(3492-3392 a B.P.),E4(2031-1894 a B.P.),and E5(1384-1321 a B.P.).E1-E4 had shown a good consistency with the paleo-earthquake recorded by the trench,and whereas E5 is a newly identified seismic event,further improving the continuous earthquake sequence of the Litang fault.Based on existing trench data and the seismic event record from the Cunge sag pond,a total of 11 paleo-earthquakes are identified along the Litang fault since the Holocene.The paleo-earthquake activity of the Litang fault exhibits a clustered pattern,with recurrence intervals of both long periods(1000 a)and short periods(500 a).Since 5000 a,the interval between strong earthquake recurrences gradually decreases,indicating an increasing risk of strong earthquakes along the Litang fault.This study presents a continuous record of paleo-earthquakes along the Litang fault,eastern Tibetan Plateau,and can enhance the understanding of regional seismic activity.展开更多
Objective:To identify chromatin regulators(CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence(BCR)after radical prostatectomy(RAP)in prostate cancer(PCa)patients.Methods:Dif...Objective:To identify chromatin regulators(CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence(BCR)after radical prostatectomy(RAP)in prostate cancer(PCa)patients.Methods:Differentially expressed genes(DEGs)between tumor and normal samples from The Cancer Genome Atlas(TCGA)and gene expression omnibus(GEO)databases were intersected with CR-related and prognostic genes.Consensus clustering,risk score analysis,functional analysis,immune microenvironment,m6A,and heterogeneity assessments were performed using R software.In vitro validation used DU145 and C42B PCa cell lines.Topoisomerase II alpha(TOP2A)was knocked down via si RNA.Assays included CCK-8 proliferation,colony formation,transwell migration/invasion,wound healing,and western blotting(WB)for pathway validation.Results:TOP2A and peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PPARGC1A)defined molecular subtypes and a risk score in TCGA,validated in a GEO dataset.Cluster 2 exhibited significantly shorter BCR-free survival vs.cluster 1 in TCGA[hazard ratio(HR):2.21;95%confidence interval(95%CI):1.32-3.73;P=0.003],GEO(HR:2.05;95%CI:1.05-4.02;P=0.010),and MSKCC2010(HR:5.93;95%CI:1.96-17.87;P<0.001).Similar survival differences were observed between high-and low-risk groups(defined by the median risk score).Cluster 2 showed greater tumor heterogeneity and higher m6A gene expression.Gene set variation analysis(GSVA)revealed downregulated cell-cycle pathways in cluster 2,alongside suppressed tumor-infiltrating immune cells.TOP2A knockdown significantly impaired PCa cell proliferation,colony formation,migration,and invasion.Mechanistically,it suppressed phosphoinositide 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)pathway activation,reducing phosphorylated PI3K and AKT levels without altering total protein.Conclusions:TOP2A and PPARGC1A effectively stratify PCa subtypes for RAP patients.TOP2A drives malignant progression via the PI3K/AKT pathway.展开更多
In the construction and maintenance for large space equipment,it is essential to ensure the control accuracy and improve the dexterity of the space manipulator.In this paper,a FiniteTime Convergence Kinematic Control(...In the construction and maintenance for large space equipment,it is essential to ensure the control accuracy and improve the dexterity of the space manipulator.In this paper,a FiniteTime Convergence Kinematic Control(FTCKC)added with Acceleration Level Dexterity Optimization(ALDO)scheme is proposed to solve the kinematic uncertainty and dexterity optimization problems of redundant space manipulators.Concretely,distinguishing from the asymptotic convergence property of traditional adaptive Jacobian methods,the FTCKC scheme is adopted to construct the equality constraint to address the model uncertainty problem,and its error can converge within a finite time.Subsequently,the dexterity index is reconstructed at acceleration level by a multi-level target handling method.Then,the equality constraint,optimization task,and limit constraints are reformulated as a quadratic programming problem.Moreover,a Recurrent Neural Network(RNN)is engineered for the constructed FTCKC-ALDO scheme.Finally,the superiority of the FTCKC-ALDO-RNN scheme is verified by experiments.展开更多
Knowledge graphs often suffer from sparsity and incompleteness.Knowledge graph reasoning is an effective way to address these issues.Unlike static knowledge graph reasoning,which is invariant over time,dynamic knowled...Knowledge graphs often suffer from sparsity and incompleteness.Knowledge graph reasoning is an effective way to address these issues.Unlike static knowledge graph reasoning,which is invariant over time,dynamic knowledge graph reasoning is more challenging due to its temporal nature.In essence,within each time step in a dynamic knowledge graph,there exists structural dependencies among entities and relations,whereas between adjacent time steps,there exists temporal continuity.Based on these structural and temporal characteristics,we propose a model named“DKGR-DR”to learn distributed representations of entities and relations by combining recurrent neural networks and graph neural networks to capture structural dependencies and temporal continuity in DKGs.In addition,we construct a static attribute graph to represent entities’inherent properties.DKGR-DR is capable of modeling both dynamic and static aspects of entities,enabling effective entity prediction and relation prediction.We conduct experiments on ICEWS05-15,ICEWS18,and ICEWS14 to demonstrate that DKGR-DR achieves competitive performance.展开更多
Northeast China serves as an important crop production region.Accurately forecasting summer precipitation in Northeast China(NEC-PR)has been a challenge due to its wide range of time scales influenced by varying clima...Northeast China serves as an important crop production region.Accurately forecasting summer precipitation in Northeast China(NEC-PR)has been a challenge due to its wide range of time scales influenced by varying climatic conditions.This study presents a scale separation hybrid statistical model with recurrent neural network(SS-RNN)to predict the summer monthly NEC-PR.The SS-RNN model decomposes the multiple scales of the NEC-PR into several spatiotemporal intrinsic mode functions covering annual to decadal time scales.This strategy provides a way to derive appropriate predictors and establish predictive models for the primary spatial modes of the NEC-PR at various time scales.Our results demonstrate substantial improvements by the SS-RNN model in predicting the summer monthly NEC-PR as compared with dynamic models,particularly in predicting the spatial pattern of the NEC-PR.In this paper we take August,the month of the highest NEC-PR,to assess our model skill.Independent forecasts of the August NEC-PR over the period 2021–24 achieve significant spatial anomaly correlation coefficients,reaching a maximum value of 0.83.Additional verifications by station observations show that the model hits most station anomalies,achieving a mean predictive skill score of 90.展开更多
基金Supported by the Grants From Department of Health, National Science Council, Executive Yuan, Taiwan (NSC-89-2314-B-195-027), China
文摘AIM: To investigate whether the changes of gap junction gene connexin messenger RNA in the noncancerous liver tissue of patients with hepatocellular carcinoma (HCC) could play a significant role in its postresection recurrence.METHODS: Seventy-nine consecutive patients having undergone curative resection for HCC entered this study.Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, connexin (Cx) 26, connexin (Cx)32 and connexin (Cx) 43 mRNAs were determined prospectively in noncancerous liver tissues from these 79 patients and in the liver tissues from 15 controls. The correlations between connexin mRNA expression and the clinicopathological variables and outcomes (tumor recurrence and recurrence related mortality) were studied.RESULTS: Compared with liver tissues of control patients,the expression of Cx 32 mRNA in noncancerous liver tissues was significantly lower (mean: 0.715 vscontrol 1.225,P＜0.01), whereas the decreased Cx 26 mRNA (mean:0.700 vs of control 1.205,P＞0.05) and increased Cx 43 mRNA (mean: 0.241 vscontrol 0.100, P＞0.05) had no statistical significance. We defined the value of Cx 32 mRNA or Cx 26mRNA below 0.800 as a lower value. By multivariate analysis for noncancerous livers, a lower value of Cx 32 mRNA correlated significantly with a risk of HCC recurrence and recurrence-related mortality. The lower value of Cx 26 mRNA did not correlate with recurrence and mortality. The increased value of Cx43 mRNA also did not correlate with postoperative recurrence and recurrence-related mortality. By multivariate analysis, other significant predictors of HCC recurrence included vascular permeation, cellular dedifferentiation, and less encaps-ulation. The other significant parameter of recurrence related mortality was vascular permeation.CONCLUSION: The decreased expression of Cx 32 mRNA in noncancerous liver tissues plays a significant role in the prediction of postoperative recurrence of HCC.
基金Project supported by the National Natural Science Foundation of China(NSFC)(Grant No.12004309)the Shaanxi Fundamental Science Research Project for Mathematics and Physics(Grant No.22JSQ036)the Scientific Research Program funded by Shaanxi Provincial Education Department(Grant No.20JK0947).
文摘We show that the nonlinear stage of the dual-wavelength pumped modulation instability(MI)in nonlinear Schrödinger equation(NLSE)can be effectively analyzed by mode truncation methods.The resulting complicated heteroclinic structure of instability unveils all possible dynamic trajectories of nonlinear waves.Significantly,the latticed-Fermi-Pasta-Ulam recurrences on the modulated-wave background in NLSE are also investigated and their dynamic trajectories run along the Hamiltonian contours of the heteroclinic structure.It is demonstrated that there has much richer dynamic behavior,in contrast to the nonlinear waves reported before.This novel nonlinear wave promises to inject new vitality into the study of MI.
文摘Let A∈N,B∈Z with gcd(A,B)=1,B{-1,0,1}. For the binary recurrence (Lucas sequence) of the form u 0=0, u 1=1, u n+2 =Au n+1 +Bu n, let N 1(A,B,k) be the number of the terms n of |u n|=k, where k∈N. In this paper, using a new result of Bilu, Hanrot and Voutier on primitive divisors, we proved that N 1(A,B,k)≤1 except N 1(1,-2,1)=5[n=1,2,3,5,13], N 1(1,-3,1)=3, N 1(1,-5,1)=3,N 1(1,B,1)=2(B{-2,-3,-5}), N 1(12,-55,1)=2, N 1(12,-377,1)=2, N 1(A,B,1)=2(A 2+B=±1, A>1), N 1(1,-2,3)=2, N 1(A,B,A)=2(A 2+2B=±1,A>1. For Lehmer sequence, we got a similar result. In addition, we also obtained some applications of the above results to some Diophantime equations.
文摘Early recurrence of atrial arrhythmias(ERAA) after ablation is common and strongly predicts late recurrences and ablation failure. However, since arrhythmia may eventually resolve in up to half of patients with ERAA, guidelines do not recommend immediate reintervention for ERAA episodes occurring during a 3-mo postablation blanking period. Certain clinical demographic, electrophysiologic, procedural, and ERAA-related characteristics may predict a higher likelihood of longterm ablation failure. In this review, we aim to discuss potential mechanisms of ERAA, and to summarize the clinical significance, prognostic implications, and treatment options for ERAA.
文摘AIM： To evaluate a series of patients with hepatocellular carcinoma （HCC） treated with several different protocols and devices. METHODS： We treated 138 patients [chronic hepatitis/ liver cirrhosis （Child-Pugh A/B/C）, 3/135 （107/25/3）] with two different devices and protocols： cool-tip needle [initial ablation at 60 W （standard method） （n = 37） or at 40 W （modified method） （n = 28）] or; ablation with a LeVeen needle using a standard single-step, full expansion （single-step） method （n = 39） or a multi-step, incremental expansion （multi-step） method. RESULTS： Eleven patients experienced rapid and scattered recurrences 1 to 7 mo after the ablation. Nine patients were treated by the cool-tip original protocol （60 W） （9/37 = 24%） and the other two by the LeVeen single-step method （2/39 = 5%）. The location of the recurrence was surrounding and limited to the site of ablation segment in three cases, and spread over one Iobule or both Iobules in the other eight cases. There was no recurrence in the patients treated with the modified cool-tip modified method （40 W） or the LeVeen multi-step method. CONCLUSION： There is a risk of rapid and scattered recurrence after RFA, especially when the standard cool- tip procedure is used. Because such recurrence would worsen the prognosis, we recommend that modified protocols for the cool-tip and LeVeen needle methods should be used in clinical practice.
基金supported by the National "863" High‐Tech Res & Dev Program of China (No. 2007AA02Z4B8)the National Science Foundation for Young Scholars of China (No. 81101745)
文摘Objective: Most recurrent intrahepatic cholangiocarcinoma (RICC) lost the opportunity of radical resection while most nonsurgical management failed to prolong patients’ survival. The efficacy and safety of radiofrequency ablation (RFA) as a local treatment for recurrent hepatocellular carcinoma have been confirmed by many clinical studies. The purpose of this study was to evaluate the efficacy, long-term survival and complications of RFA for RICC. Methods: A total of 12 patients with 19 RICCs after radical resection were included in this study. The tumors were 1.9–6.8 cm at the maximum diameter (median, 3.2±1.6 cm). All patients were treated with ultrasound guided RFA. There were two RFA approaches including percutaneous and open. Results: A total of 18 RFA treatment sessions were performed. Ablation was successful (evaluated by 1-month CT after the initial RFA procedure) in 18 (94.7%) of 19 tumors. By a median follow-up period of 29.9 months after RFA, 5 patients received repeated RFA because of intrahepatic lesion recurrence. The median local recurrence-free survival period and median event-free survival period after RFA were 21.0 months and 13.0 months, respectively. The median overall survival was 30 months, and the 1- and 3-year survival rates were 87.5% and 37.5%, respectively. The complication rate was 5.6% (1/18 sessions). The only one major complication was pleural effusion requiring thoracentesis. Conclusion: This study showed RFA may effectively and safely manage RICC with 3-year survival of 37.5%. It provides a treatment option for these RICC patients who lost chance for surgery.
文摘AIM:To analyze the anatomical and functional outcomes in the inferior recurrences of rhegmatogenous retinal detachment(RRD)depending on the surgical approach.METHODS:Eighty-one eyes of 81 patients(47 males and 34 females with a mean age of 54.8±14.1y)who demonstrated at least one inferior recurrence of RRD were included in this retrospective study.All patients were categorized as having received either circular scleral buckling(SB),pars plana vitrectomy(PPV),a combination of SB and PPV(SB+PPV),PPV with retinotomy(PPV+RT),or PPV+RT and short-term postoperative perfluorocarbon liquid tamponade(PPV+RT+pPFCL).All cases were followed up until successful retinal reattachment or third recurrence.The primary outcome measures were the achievement of the surgical goal without recurrence of RRD and bestcorrected visual acuity(BCVA).RESULTS:After the treatment of the first recurrence,the recurrence rate in the PPV+SB group was statistically significantly lower than that of the PPV(P=0.0012),PPV+RT(P=0.028),or PPV+RT+pPFCL(P=0.047)group.There was no statistically significant difference between PPV+SB,PPV+RT,and PPV+RT+pPFCL groups in the recurrence rate after treatment of the second recurrence(42 eyes).However,there was a statistically significant(P=0.016)trend towards a decrease of recurrence rate after PPV+RT+pPFCL.There was no statistically significant improvement of BCVA in either study group(P>0.05)after both first and second recurrence surgery.The mean time follow-up was 109.0±91.0d before the first recurrence and 210.0±186.6d between previous surgery at second recurrence.CONCLUSION:Patients with first inferior recurrence of RRD may benefit from SB as an adjunct to PPV.RT and short-term pPFCL tamponade in the second recurrence may allow better anatomical outcomes,however,without functional improvement.
文摘AIM: To investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence.METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohn’s disease (CD) in our center (1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy (median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy.RESULTS: From 205 patients who underwent surgery, 161 patients (follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype (B3) were postoperative risk factors. Previous perianal abscess/fistula (other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management (n = 49/161) prevented clinical (HR = 0.4, 95%CI: 0.25-0.66, P < 0.001) and surgical postoperative recurrence (HR = 0.30, 95%CI: 0.13-0.70, P = 0.006).CONCLUSION: Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation.
文摘Background: Bacterial vaginosis (BV) is the most common urogenital disease in women, affecting about 19% - 24% of them in reproductive ages annually and after treatment, a single recurrence or more may occur in up to 58% of women within 12 months. Objective: The aim was to evaluate the effectiveness of a new orally administered food supplement, containing different probiotic strains, on women of childbearing age after the antibiotic treatment when compared with no probiotic intake. Methods: A prospective study was undertaken on 62 patients with BV. All patients were cured with metronidazole vaginal formulations (5 g of 0.75% gel once daily for 5 days or 500 mg ovules once daily for 7 days), then after was offered the option of using a new an orally administered food supplement containing: Lactobacillus plantarum PBS067, Lactobacillus rhamnosus LRH020 and Bifidobacterium animalis lactis BL050, with a total viability of 3 × 109 CFU/capsule (Intimique®Femme). Among these women, 50 accepted to use the new orally food supplement, while 25 patients decided to use only metronidazole (control group). Results: The recurrence rate of BV after treatment with Intimique®Femme was about 16%, compared to 40% in the control group. The incidence of abnormal vaginal microbiota decreased in both groups, but it was significantly higher in the Intimique®Femme group at the end of treatment. Conclusion: This study showed that, in case of BV diagnosis, the complementary treatment of a strain-specific probiotic complex after antibiotics prophylaxis, is mandatory to reduce potential recurrences and cyclic use of further antibiotics.
文摘We report a case of myxoma with multiple recurrences in both the atrium and ventricle in a 26-year-old woman five years after the surgical removal of left atrial myxoma, Her 52-year-old mother had a similar medical history. To our knowledge, this was the first familial case who suffered multifocal cardiac myxoma recurrences without any sign of the myxoma complex. Based on our understanding of the mechanism of recurrence, the approaches to prevent the recurrence, and markers to predict recurrence, we propose that multifocal recurrences, as reported herein, may result from a combination of familial predisposition and multifocal onset. The hi-atrial surgical approach and transesophageal echocardiography are preferred for patients with recurrent cardiac myxomas, especially for those with multiple recurrences and familial myxoma. Immunological and genetic screenings may help to identify family members at risk for developing this disease.
文摘Background: Sentinel node biopsy (SNB) was introduced at Ullevaal University Hospital in 2000. This article presents results from the first ten years use of the method. Material and Methods: A prospective registration of 2762 patients was made from 2000 through 2009. Results: The median follow-up time was 51 months. The overall detection rate was 93%. 36% of the patients with positive SNs had non-sentinel metastases. These were significantly associated with a macrometastatic SN and a primary tumour>20 mm. 18% of patients with sentinel metastasis≤2 mm had non-sentinel metastases. 14 patients with negative SN (0.7%) developed axillary recurrence. 32% with a preoperative diagnosis of ductal carcinoma in situ (DCIS) were upstaged to infiltrating carcinoma on final histology. None of the patients with pure DCIS had positive SNs. Conclusion: Few late events (0.7%) in SN negative axillas demonstrate the safety of the technique.
文摘Recurrent pregnancy loss(RPL)affects 2%-5%of couples attempting to conceive.It is a highly heterogenous condition attributed to several factors including endocrine dysfunction,auto immune disorders,thrombophilia,genetic abnormalities,infectious diseases,uterine anomalies,sperm DNA fragmentation,and epigenetics.Among genetic causes,chromosomal abnormalities are the most frequent etiological factor of early miscarriage,accounting for 50%–60%of first trimester abortions.Numerical or structural chromosomal changes may result in spontaneous miscarriages.These anomalies arise as a result of chromosomal translocation,non-disjunction,or mutations[1].Transmission of parental chromosomal abnormalities may be one of the chances for a recurrence of miscarriage in the first trimester of pregnancy,albeit the cause is unknown[2,3].
文摘Objectives:Tumor recurrence is a major determinant of poor prognosis in hepatocellular carcinoma(HCC),yet its cellular and molecular basis remains incompletely understood.This study aimed to identify recurrenceassociated genes at single-cell resolution and to develop a prognostic model for predicting survival outcomes and immunotherapy responsiveness in HCC.Methods:Single-cell RNA sequencing data from 12 primary and 6 recurrent HCC samples were integrated and analyzed to identify genes characteristic of recurrence.After quality control,principal component analysis,and t-SNE-based clustering were used to identify highly variable genes for cell clustering and annotation.Based on macrophage characteristic genes,a recurrence-related risk score was constructed using a LASSOCox regression model,and a nomogram integrating clinical variables was developed.Prognostic performance was assessed using Kaplan-Meier analysis and time-dependent ROC curves.Immune infiltration profiling was performed to compare immune characteristics between risk groups defined by the prognostic model.Multivariate Cox regression was applied to identify independent prognostic biomarkers,which were subsequently validated by cell function experiments.Results:The risk model effectively stratified patients into high-and low-risk groups with distinct survival outcomes,demonstrating high predictive accuracy for 1-,3-,and 5-year survival.High-risk patients showed altered immune profiles and a reduced predicted response to immunotherapy.GRID2,RNF186,and SLC4A10 were identified as independent prognostic genes,with RNF186 promoting HCC cell proliferation in a SESN2-dependent manner.Conclusion:This prognostic model provides new insights into precision medicine and immunotherapy for HCC,highlighting the potential clinical significance of RNF186 as a therapeutic target.
基金Supported by grants from the National Natural Science Foundation of China(No.82171018,No.82371022)Beijing Hospitals Authority’s Ascent Plan(No.DFL20240202)+2 种基金The Youth Beijing Scholars Program(No.022)High Level Public Health Technical Talents Construction Project from Beijing(Jie Y)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(No.2023YFC2410401).
文摘AIM:To evaluate the efficacy and safety of decellularized conjunctival stroma(DCS)as a novel biomaterial by comparing its grafting outcomes with amniotic membrane(AM)when used for conjunctival reconstruction after primary pterygium excision.METHODS:This randomized,parallel-controlled study with allocation concealment enrolled 40 patients with primary pterygium.Participants were randomly assigned to two groups using the sealed envelope method:the DCS group(n=20)and the AM group(n=18),receiving DCS and AM grafts respectively.Slit-lamp photography of the operative eyes was performed preoperatively and at 1,3,5,7,10,30,90,and 180d postoperatively.Best-corrected visual acuity(BCVA)and symptom scores were recorded simultaneously.In vivo confocal microscopy was conducted at 3 and 6mo postoperatively.RESULTS:All participants exhibited improved postoperative symptoms.The mean age was 60±9y(male/female ratio:6/14)in the DCS group and 56±12y(male/female ratio:7/11)in the AM group.The average epithelial healing time was 9.89±3.54d in the DCS group and 8.17±1.34d in the AM group(P=0.084).One recurrence case was observed in each group.Postoperative graft hemorrhage was significantly more severe in the DCS group than in the AM group only at 30d postoperatively(P=0.011).In vivo confocal microscopy revealed conjunctival epithelial cell growth in both groups at 90d postoperatively,while clear corneo-conjunctival cell boundaries were observed until 180d postoperatively.CONCLUSION:DCS used in primary pterygium surgery has a safety profile comparable to AM.It promotes rapid postoperative conjunctival healing,achieves a relatively low pterygium recurrence rate,and yields outcomes similar to AM.DCS provides a novel biomaterial option for conjunctival reconstruction after pterygium excision and the treatment of other conjunctival injuries.
基金supported by the Scientific Research Program Funded by Shaanxi Provincial Education Department(Program No.23JP100)the Key Natural Science Research Project of Shaanxi Energy Institute:Comprehensive Characterization Study of Lithium-Ion Batteries for New Energy Vehicles(Project No.23QNZRZ01).
文摘The accurate state of health(SOH)estimation in lithium-ion batteries represents a critical technological challenge with profound implications for electric vehicle performance and user experience.Precise SOH assessment not only enables reliable mileage prediction but also ensures operational safety.However,the complex and non-linear capacity fading process during battery cycling poses a challenge to obtaining accurate SOH.To address this issue,this study proposes an effective health factor derived from the local voltage range during the battery charging phase.First,the battery charging phase is divided evenly with reference to voltage intervals,and an importance analysis is conducted on each voltage interval.From these,the voltage interval with the strongest correlation to State of Health(SOH)is extracted as the feature interval.Then,a data-driven framework integrating variational mode decomposition(VMD)with gated recurrent unit(GRU)neural networks enables comprehensive multi-scale temporal feature analysis for enhanced SOH estimation.The methodology begins with rigorous feature engineering to identify and extract optimal health indicators demonstrating superior correlation.Subsequently,the VMD algorithm performs sophisticated signal processing to decompose both the measured capacity and derived health indicators into their constituent intrinsic mode functions and residual components.Finally,a GRU-based neural network is implemented to establish a robust SOH estimation model.Experimental validation using cycling data from different datasets shows that the root mean square error of the estimation results is consistently below 3%,demonstrating the good accuracy and generalisation of the proposed method,using only local data from the charging phase.
基金supported by the National Natural Science Foundation of China(42202131 and 42177184).
文摘This study examines a 1.32 m thick sediment sequence from the Cunge sag pond in the Litang Basin,eastern Tibetan Plateau,to assess the seismicity of the Litang fault during the Holocene.High-resolution geochemical,grain size,magnetic susceptibility,and total organic carbon indicators are employed to obtain a continuous record of changes in elemental,physical,and biological properties within the profile to identify seismic events.The seismic event layer generally comprises two sedimentary rhythms:a lower coarse sand layer and an upper fine silt-clay layer.These layers represent rapid deposition associated with fault activity(Earthquake A)and slower deposition during calm periods or earthquake recurrence intervals(Seismic interval A).Through six^(14)C dating,five seismic events have been identified in the Cunge sag pond section:E1(before 3955 a B.P.),E2(3713-3703 a B.P.),E3(3492-3392 a B.P.),E4(2031-1894 a B.P.),and E5(1384-1321 a B.P.).E1-E4 had shown a good consistency with the paleo-earthquake recorded by the trench,and whereas E5 is a newly identified seismic event,further improving the continuous earthquake sequence of the Litang fault.Based on existing trench data and the seismic event record from the Cunge sag pond,a total of 11 paleo-earthquakes are identified along the Litang fault since the Holocene.The paleo-earthquake activity of the Litang fault exhibits a clustered pattern,with recurrence intervals of both long periods(1000 a)and short periods(500 a).Since 5000 a,the interval between strong earthquake recurrences gradually decreases,indicating an increasing risk of strong earthquakes along the Litang fault.This study presents a continuous record of paleo-earthquakes along the Litang fault,eastern Tibetan Plateau,and can enhance the understanding of regional seismic activity.
基金supported by the funding of Chinese Scholarship Council(No.202206240086)。
文摘Objective:To identify chromatin regulators(CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence(BCR)after radical prostatectomy(RAP)in prostate cancer(PCa)patients.Methods:Differentially expressed genes(DEGs)between tumor and normal samples from The Cancer Genome Atlas(TCGA)and gene expression omnibus(GEO)databases were intersected with CR-related and prognostic genes.Consensus clustering,risk score analysis,functional analysis,immune microenvironment,m6A,and heterogeneity assessments were performed using R software.In vitro validation used DU145 and C42B PCa cell lines.Topoisomerase II alpha(TOP2A)was knocked down via si RNA.Assays included CCK-8 proliferation,colony formation,transwell migration/invasion,wound healing,and western blotting(WB)for pathway validation.Results:TOP2A and peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PPARGC1A)defined molecular subtypes and a risk score in TCGA,validated in a GEO dataset.Cluster 2 exhibited significantly shorter BCR-free survival vs.cluster 1 in TCGA[hazard ratio(HR):2.21;95%confidence interval(95%CI):1.32-3.73;P=0.003],GEO(HR:2.05;95%CI:1.05-4.02;P=0.010),and MSKCC2010(HR:5.93;95%CI:1.96-17.87;P<0.001).Similar survival differences were observed between high-and low-risk groups(defined by the median risk score).Cluster 2 showed greater tumor heterogeneity and higher m6A gene expression.Gene set variation analysis(GSVA)revealed downregulated cell-cycle pathways in cluster 2,alongside suppressed tumor-infiltrating immune cells.TOP2A knockdown significantly impaired PCa cell proliferation,colony formation,migration,and invasion.Mechanistically,it suppressed phosphoinositide 3-kinase(PI3K)/AKT serine/threonine kinase(AKT)pathway activation,reducing phosphorylated PI3K and AKT levels without altering total protein.Conclusions:TOP2A and PPARGC1A effectively stratify PCa subtypes for RAP patients.TOP2A drives malignant progression via the PI3K/AKT pathway.
基金supported by the National Natural Science Foundation of China(Nos.92148203 and T2388101)。
文摘In the construction and maintenance for large space equipment,it is essential to ensure the control accuracy and improve the dexterity of the space manipulator.In this paper,a FiniteTime Convergence Kinematic Control(FTCKC)added with Acceleration Level Dexterity Optimization(ALDO)scheme is proposed to solve the kinematic uncertainty and dexterity optimization problems of redundant space manipulators.Concretely,distinguishing from the asymptotic convergence property of traditional adaptive Jacobian methods,the FTCKC scheme is adopted to construct the equality constraint to address the model uncertainty problem,and its error can converge within a finite time.Subsequently,the dexterity index is reconstructed at acceleration level by a multi-level target handling method.Then,the equality constraint,optimization task,and limit constraints are reformulated as a quadratic programming problem.Moreover,a Recurrent Neural Network(RNN)is engineered for the constructed FTCKC-ALDO scheme.Finally,the superiority of the FTCKC-ALDO-RNN scheme is verified by experiments.
基金supported byNationalNatural Science Foundation of China(GrantNos.62071098,U24B20128)Sichuan Science and Technology Program(Grant No.2022YFG0319).
文摘Knowledge graphs often suffer from sparsity and incompleteness.Knowledge graph reasoning is an effective way to address these issues.Unlike static knowledge graph reasoning,which is invariant over time,dynamic knowledge graph reasoning is more challenging due to its temporal nature.In essence,within each time step in a dynamic knowledge graph,there exists structural dependencies among entities and relations,whereas between adjacent time steps,there exists temporal continuity.Based on these structural and temporal characteristics,we propose a model named“DKGR-DR”to learn distributed representations of entities and relations by combining recurrent neural networks and graph neural networks to capture structural dependencies and temporal continuity in DKGs.In addition,we construct a static attribute graph to represent entities’inherent properties.DKGR-DR is capable of modeling both dynamic and static aspects of entities,enabling effective entity prediction and relation prediction.We conduct experiments on ICEWS05-15,ICEWS18,and ICEWS14 to demonstrate that DKGR-DR achieves competitive performance.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFC3002803)the National Key Research and Development Program of China(Grant No.2024YFF0808402)the National Natural Science Foundation of China(Grant No.42375169)。
文摘Northeast China serves as an important crop production region.Accurately forecasting summer precipitation in Northeast China(NEC-PR)has been a challenge due to its wide range of time scales influenced by varying climatic conditions.This study presents a scale separation hybrid statistical model with recurrent neural network(SS-RNN)to predict the summer monthly NEC-PR.The SS-RNN model decomposes the multiple scales of the NEC-PR into several spatiotemporal intrinsic mode functions covering annual to decadal time scales.This strategy provides a way to derive appropriate predictors and establish predictive models for the primary spatial modes of the NEC-PR at various time scales.Our results demonstrate substantial improvements by the SS-RNN model in predicting the summer monthly NEC-PR as compared with dynamic models,particularly in predicting the spatial pattern of the NEC-PR.In this paper we take August,the month of the highest NEC-PR,to assess our model skill.Independent forecasts of the August NEC-PR over the period 2021–24 achieve significant spatial anomaly correlation coefficients,reaching a maximum value of 0.83.Additional verifications by station observations show that the model hits most station anomalies,achieving a mean predictive skill score of 90.
