In this paper,ambient IoT is used as a typical use case of massive connections for the sixth generation(6G)mobile communications where we derive the performance requirements to facilitate the evaluation of technical s...In this paper,ambient IoT is used as a typical use case of massive connections for the sixth generation(6G)mobile communications where we derive the performance requirements to facilitate the evaluation of technical solutions.A rather complete design of unsourced multiple access is proposed in which two key parts:a compressed sensing module for active user detection,and a sparse interleaver-division multiple access(SIDMA)module are simulated side by side on a same platform at balanced signal to noise ratio(SNR)operating points.With a proper combination of compressed sensing matrix,a convolutional encoder,receiver algorithms,the simulated performance results appear superior to the state-of-the-art benchmark,yet with relatively less complicated processing.展开更多
●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features ...●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS.However,as the number of reported cases increases,secondary MEWDS occurs in other related retinal diseases and injuries,exhibiting some special characteristics.The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy(MFC/PIC),acute zonal occult outer retinopathy,best vitelliform macular dystrophy,pseudoxanthoma elasticum,and ocular toxoplasmosis.The related retinal injury is laser photocoagulation,surgery,and trauma.Although primary MEWDS often have a self-limiting course,secondary MEWDS may require treatment in some cases,according to the severity of concomitant diseases and complications.Notably,MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation,needs positive treatment with corticosteroids.The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch’s membrane.The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances.Its prognosis and treatment depend on the severity of complications.Current studies propose that the etiology is associated with immune factors,including viral infection,inflammation in choroid and Bruch’s membrane,and antigen exposure caused by retinal and/or choroidal insults.More pathogenic studies should be conducted in the future.Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.展开更多
BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal...BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal-onset form without congenital anomalies.Type III is considered to a milder form and usually responds to riboflavin.However,late-onset form could also be fatal and not responsive to treatments.CASE SUMMARY We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction.Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected.Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal,revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient.By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects,a rare ETFDH gene variant was identified:NM_004453:4:C.1448C>T(p.Pro483 Leu).The patient was diagnosed with lateonset GAII.He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death.CONCLUSION Type III MADD can also be fatal and not responsive to treatments.展开更多
The fatigue damage caused by flow-induced vibration(FIV)is one of the major concerns for multiple cylindrical structures in many engineering applications.The FIV suppression is of great importance for the security of ...The fatigue damage caused by flow-induced vibration(FIV)is one of the major concerns for multiple cylindrical structures in many engineering applications.The FIV suppression is of great importance for the security of many cylindrical structures.Many active and passive control methods have been employed for the vibration suppression of an isolated cylinder undergoing vortex-induced vibrations(VIV).The FIV suppression methods are mainly extended to the multiple cylinders from the vibration control of the isolated cylinder.Due to the mutual interference between the multiple cylinders,the FIV mechanism is more complex than the VIV mechanism,which makes a great challenge for the FIV suppression.Some efforts have been devoted to vibration suppression of multiple cylinder systems undergoing FIV over the past two decades.The control methods,such as helical strakes,splitter plates,control rods and flexible sheets,are not always effective,depending on many influence factors,such as the spacing ratio,the arrangement geometrical shape,the flow velocity and the parameters of the vibration control devices.The FIV response,hydrodynamic features and wake patterns of the multiple cylinders equipped with vibration control devices are reviewed and summarized.The FIV suppression efficiency of the vibration control methods are analyzed and compared considering different influence factors.Further research on the FIV suppression of multiple cylinders is suggested to provide insight for the development of FIV control methods and promote engineering applications of FIV control methods.展开更多
Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow d...Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.展开更多
In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible ...In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.展开更多
Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple rol...Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.展开更多
The efficient separation and collection of ammonia(NH_(3))during NH_(3) synthesis process is essential to improve the economic efficiency and protect the environment.In this work,ethanolammonium hydrochloride(EtOHACl)...The efficient separation and collection of ammonia(NH_(3))during NH_(3) synthesis process is essential to improve the economic efficiency and protect the environment.In this work,ethanolammonium hydrochloride(EtOHACl)and phenol(PhOH)were used to prepare a novel class of deep eutectic solvents(DESs)with multiple active sites and low viscosities.The NH_(3) separation performance of EtOHACl+PhOH DESs was analyzed completely.It is figured out that the NH_(3) absorption rates in EtOHACl+PhOH DESs are very fast.The NH_(3) absorption capacities are very high and reach up to 5.52 and 10.74 mol·kg1 at 11.2 and 100.4 kPa under 298.2 K,respectively.In addition,the EtOHACl+PhOH DESs present highly selective absorption of NH_(3) over N_(2) and H_(2) and good regenerative properties after seven cycles of absorption/desorption.The intrinsic separation mechanism of NH_(3) by EtOHACl+PhOH DESs was further revealed by spectroscopic analysis and quantum chemistry calculations.展开更多
Clarifying China’s position in the global system is an important logical basis for developing national diplomacy.Although much research has been done on China’s development status,most studies have been based on cou...Clarifying China’s position in the global system is an important logical basis for developing national diplomacy.Although much research has been done on China’s development status,most studies have been based on country comparisons or institutional en-vironment.In today’s networked era in which the global economy,trade,personnel,and information are closely connected,studies on China’s global position and its status changes and influencing factors in multiple contact networks are still insufficient.In this study,from the perspective of diverse global contact networks,we constructed economic,cultural,and political influence indices to explore the changes and influencing factors on China’s status in the global system from 2005 to 2018.The results show that during the study period,China’s global influence in the fields of economic ties,cultural exchanges,and political contacts increased significantly,but its influ-ence in the fields of cultural exchanges and political contacts lagged far economic ties.The pattern of China’s economic influence on various economies around the world has shown a transformation from an‘upright pyramid’to an‘inverted pyramid’structure.The proportion of these economies in low-influence zones has decreased from more than 60%in 2005 to less than 20%in 2018.China’s cultural and political influence on various economies around the world has increased significantly;however,for the former,the percentage of high-influence areas is still less than 20%,whereas for the latter the percentage of these economies in medium-and high-influence areas is still less than 50%.Analyses such as a scatter plot matrix show that geographical proximity,economic globalization,close cooperation with developing countries,and a proactive and peaceful foreign policy are important factors in improving China’s status in the diverse global network system.展开更多
This paper realizes the full-domain collaborative deployment of multiple interference sources of the global satellite navigation system(GNSS)and evaluates the deployment effect to enhance the ability to disturb the at...This paper realizes the full-domain collaborative deployment of multiple interference sources of the global satellite navigation system(GNSS)and evaluates the deployment effect to enhance the ability to disturb the attacker and the capability to defend the GNSS during navigation countermeasures.Key evaluation indicators for the jamming effect of GNSS suppressive and deceptive jamming sources are first created,their evaluation models are built,and their detection procedures are sorted out,as the basis for determining the deployment principles.The principles for collaboratively deploying multi-jamming sources are developed to obtain the deployment structures(including the required number,structures in demand,and corresponding positions)of three single interference sources required by collaboratively deploying.Accordingly,simulation and hardware-in-loop testing results are presented to determine a rational configuration of the collaborative deployment of multi-jamming sources in the set situation and further realize the full-domain deployment of an interference network from ground,air to space.Varied evaluation indices for the deployment effect are finally developed to evaluate the deployment effect of the proposed configuration and further verify its reliability and rationality.展开更多
Let X={X(t)∈R^(d),t∈R^(N)}be a centered space-time anisotropic Gaussian field with indices H=(H_(1),…,H_(N))∈(0,1)~N,where the components X_(i)(i=1,…,d)of X are independent,and the canonical metric√(E(X_(i)(t)-X...Let X={X(t)∈R^(d),t∈R^(N)}be a centered space-time anisotropic Gaussian field with indices H=(H_(1),…,H_(N))∈(0,1)~N,where the components X_(i)(i=1,…,d)of X are independent,and the canonical metric√(E(X_(i)(t)-X_(i)(s))^(2))^(1/2)(i=1,…,d)is commensurate with■for s=(s_(1),…,s_(N)),t=(t_(1),…,t_(N))∈R~N,α_(i)∈(0,1],and with the continuous functionγ(·)satisfying certain conditions.First,the upper and lower bounds of the hitting probabilities of X can be derived from the corresponding generalized Hausdorff measure and capacity,which are based on the kernel functions depending explicitly onγ(·).Furthermore,the multiple intersections of the sample paths of two independent centered space-time anisotropic Gaussian fields with different distributions are considered.Our results extend the corresponding results for anisotropic Gaussian fields to a large class of space-time anisotropic Gaussian fields.展开更多
Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three t...Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP.Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays.Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05).Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.展开更多
High-voltage circuit breakers are the core equipment in power networks,and to a certain extent,are related to the safe and reliable operation of power systems.However,their core components are prone to mechanical faul...High-voltage circuit breakers are the core equipment in power networks,and to a certain extent,are related to the safe and reliable operation of power systems.However,their core components are prone to mechanical faults.This study proposes a component separation method to detect multiple mechanical faults in circuit breakers that can achieve online real-time monitoring.First,a model and strategy are presented for obtaining mechanical voiceprint signals from circuit breakers.Subsequently,the component separation method was used to decompose the voiceprint signals of multiple faults into individual component signals.Based on this,the recognition of the features of a single-fault voiceprint signal can be achieved.Finally,multiple faults in high-voltage circuit breakers were identified through an experimental simulation and verification of the circuit breaker voiceprint signals collected from the substation site.The research results indicate that the proposed method exhibits excellent performance for multiple mechanical faults,such as spring structures and loose internal components of circuit breakers.In addition,it provides a reference method for the real-time online monitoring of high-voltage circuit breakers.展开更多
This paper presents an attempt at assimilating clear-sky FY-4A Advanced Geosynchronous Radiation Imager(AGRI)radiances from two water vapor channels for the prediction of three landfalling typhoon events over the West...This paper presents an attempt at assimilating clear-sky FY-4A Advanced Geosynchronous Radiation Imager(AGRI)radiances from two water vapor channels for the prediction of three landfalling typhoon events over the West Pacific Ocean using the 3DVar data assimilation(DA)method along with the WRF model.A channel-sensitive cloud detection scheme based on the particle filter(PF)algorithm is developed and examined against a cloud detection scheme using the multivariate and minimum residual(MMR)algorithm and another traditional cloud mask–dependent cloud detection scheme.Results show that both channel-sensitive cloud detection schemes are effective,while the PF scheme is able to reserve more pixels than the MMR scheme for the same channel.In general,the added value of AGRI radiances is confirmed when comparing with the control experiment without AGRI radiances.Moreover,it is found that the analysis fields of the PF experiment are mostly improved in terms of better depicting the typhoon,including the temperature,moisture,and dynamical conditions.The typhoon track forecast skill is improved with AGRI radiance DA,which could be explained by better simulating the upper trough.The impact of assimilating AGRI radiances on typhoon intensity forecasts is small.On the other hand,improved rainfall forecasts from AGRI DA experiments are found along with reduced errors for both the thermodynamic and moisture fields,albeit the improvements are limited.展开更多
How to effectively evaluate the firing precision of weapon equipment at low cost is one of the core contents of improving the test level of weapon system.A new method to evaluate the firing precision of the MLRS consi...How to effectively evaluate the firing precision of weapon equipment at low cost is one of the core contents of improving the test level of weapon system.A new method to evaluate the firing precision of the MLRS considering the credibility of simulation system based on Bayesian theory is proposed in this paper.First of all,a comprehensive index system for the credibility of the simulation system of the firing precision of the MLRS is constructed combined with the group analytic hierarchy process.A modified method for determining the comprehensive weight of the index is established to improve the rationality of the index weight coefficients.The Bayesian posterior estimation formula of firing precision considering prior information is derived in the form of mixed prior distribution,and the rationality of prior information used in estimation model is discussed quantitatively.With the simulation tests,the different evaluation methods are compared to validate the effectiveness of the proposed method.Finally,the experimental results show that the effectiveness of estimation method for firing precision is improved by more than 25%.展开更多
Conservative chaotic systems have unique advantages over dissipative chaotic systems in the fields of secure communication and pseudo-random number generator because they do not have attractors but possess good traver...Conservative chaotic systems have unique advantages over dissipative chaotic systems in the fields of secure communication and pseudo-random number generator because they do not have attractors but possess good traversal and pseudorandomness. In this work, a novel five-dimensional(5D) Hamiltonian conservative hyperchaotic system is proposed based on the 5D Euler equation. The proposed system can have different types of coordinate transformations and time reversal symmetries. In this work, Hamilton energy and Casimir energy are analyzed firstly, and it is proved that the new system satisfies Hamilton energy conservation and can generate chaos. Then, the complex dynamic characteristics of the system are demonstrated and the conservatism and chaos characteristics of the system are verified through the correlation analysis methods such as phase diagram, equilibrium point, Lyapunov exponent, bifurcation diagram, and SE complexity. In addition, a detailed analysis of the multistable characteristics of the system reveals that many energy-related coexisting orbits exist. Based on the infinite number of center-type and saddle-type equilibrium points, the dynamic characteristics of the hidden multistability of the system are revealed. Then, the National Institute of Standards and Technology(NIST)test of the new system shows that the chaotic sequence generated by the system has strong pseudo-random. Finally, the circuit simulation and hardware circuit experiment of the system are carried out with Multisim simulation software and digital signal processor(DSP) respectively. The experimental results confirm that the new system has good ergodicity and realizability.展开更多
Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we r...Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we report a multiple redox-mediated linear paired electrolysis system,combining the hydrogen peroxide mediated cathode process with the I2 mediated anode process,and realize the conversion of furfural to furoic acid in both side of the dividedflow cell simultaneously.By reasonably controlling the cathode potential,the undesired water splitting reaction and furfural reduction side reactions are avoided.Under the galvanostatic electrolysis,the two-mediated electrode processes have good compatibility,which reduce the energy consumption by about 22%while improving the electronic efficiency by about 125%.This system provides a green electrochemical synthesis route with commercial prospects.展开更多
In the research and development of new silicon pixel detectors,a collimated monoenergetic charged-particle test beam equipped with a high-resolution pixel-beam telescope is crucial for prototype verification and perfo...In the research and development of new silicon pixel detectors,a collimated monoenergetic charged-particle test beam equipped with a high-resolution pixel-beam telescope is crucial for prototype verification and performance evaluation.When the beam energy is low,the effect of multiple Coulomb scattering on the measured resolution of the Device Under Test(DUT)must be considered to accurately evaluate the performance of the pixel chips and detectors.This study aimed to investigate the effect of multiple Coulomb scattering on the measured resolution,particularly at low beam energies.Simulations were conducted using Allpix^(2) to study the effects of multiple Coulomb scattering under different beam energies,material budgets,and telescope layouts.The simulations also provided the minimum energy at which the effect of multiple Coulomb scattering could be ignored.Compared with the results of a five-layer detector system tested with an electron beam at DESY,the simulation results were consistent with the beam test results,confirming the reliability of the simulations.展开更多
Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four R...Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.展开更多
Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response v...Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response varies among individuals.Genetic factor may play an important role in BIPN.Methods:A nextgeneration sequencing(NGS)panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy.mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR(RT-qPCR).Serum homocysteine(Hcy)levels were detected in 40 samples by chemiluminescent microparticle immunoassay(CMIA).Results:Compared with the non-BIPN group(n=89),a total of 8 significantly associated single nucleotide polymorphisms(SNPs)were identified in the BIPN group(n=115):MTHFR(rs1801131,rs1801133,rs17421511),EPHX1(rs1051740),MME(rs2016848),ALDH1A1(rs6151031),HTR7(rs1935349)and CYP2A6(rs8192720).The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment(NP group)was lower than that of newly diagnosed patients without peripheral neuritis after treatment(NnP group)(1.70±0.77 vs.2.81±0.97,p=0.009).Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group(11.66±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/L,p≤0.001).Conclusion:CYP2A6,EPHX1,MTHFR,ALDH1A1,HTR7,MME and BIPN are linked in Chinese MM patients.BIPN is more likely to occur in patients with lower MTHFR mRNA expression,which might result in higher serum Hcy levels.展开更多
文摘In this paper,ambient IoT is used as a typical use case of massive connections for the sixth generation(6G)mobile communications where we derive the performance requirements to facilitate the evaluation of technical solutions.A rather complete design of unsourced multiple access is proposed in which two key parts:a compressed sensing module for active user detection,and a sparse interleaver-division multiple access(SIDMA)module are simulated side by side on a same platform at balanced signal to noise ratio(SNR)operating points.With a proper combination of compressed sensing matrix,a convolutional encoder,receiver algorithms,the simulated performance results appear superior to the state-of-the-art benchmark,yet with relatively less complicated processing.
基金Supported by the National Natural Science Foundation of China(No.82171073No.82101147).
文摘●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS.However,as the number of reported cases increases,secondary MEWDS occurs in other related retinal diseases and injuries,exhibiting some special characteristics.The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy(MFC/PIC),acute zonal occult outer retinopathy,best vitelliform macular dystrophy,pseudoxanthoma elasticum,and ocular toxoplasmosis.The related retinal injury is laser photocoagulation,surgery,and trauma.Although primary MEWDS often have a self-limiting course,secondary MEWDS may require treatment in some cases,according to the severity of concomitant diseases and complications.Notably,MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation,needs positive treatment with corticosteroids.The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch’s membrane.The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances.Its prognosis and treatment depend on the severity of complications.Current studies propose that the etiology is associated with immune factors,including viral infection,inflammation in choroid and Bruch’s membrane,and antigen exposure caused by retinal and/or choroidal insults.More pathogenic studies should be conducted in the future.Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.
文摘BACKGROUND Multiple acyl-CoA dehydrogenase deficiency(MADD)is a disease of rare autosomal recessive disorder.There are three types of MADD.Type I is a neonatalonset form with congenital anomalies.Type II is a neonatal-onset form without congenital anomalies.Type III is considered to a milder form and usually responds to riboflavin.However,late-onset form could also be fatal and not responsive to treatments.CASE SUMMARY We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction.Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected.Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal,revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient.By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects,a rare ETFDH gene variant was identified:NM_004453:4:C.1448C>T(p.Pro483 Leu).The patient was diagnosed with lateonset GAII.He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death.CONCLUSION Type III MADD can also be fatal and not responsive to treatments.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.U2106223,51979193,52301352)。
文摘The fatigue damage caused by flow-induced vibration(FIV)is one of the major concerns for multiple cylindrical structures in many engineering applications.The FIV suppression is of great importance for the security of many cylindrical structures.Many active and passive control methods have been employed for the vibration suppression of an isolated cylinder undergoing vortex-induced vibrations(VIV).The FIV suppression methods are mainly extended to the multiple cylinders from the vibration control of the isolated cylinder.Due to the mutual interference between the multiple cylinders,the FIV mechanism is more complex than the VIV mechanism,which makes a great challenge for the FIV suppression.Some efforts have been devoted to vibration suppression of multiple cylinder systems undergoing FIV over the past two decades.The control methods,such as helical strakes,splitter plates,control rods and flexible sheets,are not always effective,depending on many influence factors,such as the spacing ratio,the arrangement geometrical shape,the flow velocity and the parameters of the vibration control devices.The FIV response,hydrodynamic features and wake patterns of the multiple cylinders equipped with vibration control devices are reviewed and summarized.The FIV suppression efficiency of the vibration control methods are analyzed and compared considering different influence factors.Further research on the FIV suppression of multiple cylinders is suggested to provide insight for the development of FIV control methods and promote engineering applications of FIV control methods.
文摘Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.
文摘In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.
基金supported by the National Natural Science Foundation of China,Nos.82060219,82271234the Natural Science Foundation of Jiangxi Province,Nos.20212ACB216009,20212BAB216048+1 种基金Jiangxi Province Thousands of Plans,No.jxsq2019201023Youth Team Project of the Second Affiliated Hospital of Nanchang University,No.2019YNTD12003(all to FH)。
文摘Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.
基金supported by the National Natural Science Foundation of China(22221005 and 22008033).
文摘The efficient separation and collection of ammonia(NH_(3))during NH_(3) synthesis process is essential to improve the economic efficiency and protect the environment.In this work,ethanolammonium hydrochloride(EtOHACl)and phenol(PhOH)were used to prepare a novel class of deep eutectic solvents(DESs)with multiple active sites and low viscosities.The NH_(3) separation performance of EtOHACl+PhOH DESs was analyzed completely.It is figured out that the NH_(3) absorption rates in EtOHACl+PhOH DESs are very fast.The NH_(3) absorption capacities are very high and reach up to 5.52 and 10.74 mol·kg1 at 11.2 and 100.4 kPa under 298.2 K,respectively.In addition,the EtOHACl+PhOH DESs present highly selective absorption of NH_(3) over N_(2) and H_(2) and good regenerative properties after seven cycles of absorption/desorption.The intrinsic separation mechanism of NH_(3) by EtOHACl+PhOH DESs was further revealed by spectroscopic analysis and quantum chemistry calculations.
基金Under the auspices of National Natural Science Foundation of China(No.42201181,42171181)Fundamental Research Funds for the Central Universities(No.2412022QD002)The Medium and Long-term Major Training Foundation of Philosophy and Social Sciences of Northeast Normal University(No.22FR006)。
文摘Clarifying China’s position in the global system is an important logical basis for developing national diplomacy.Although much research has been done on China’s development status,most studies have been based on country comparisons or institutional en-vironment.In today’s networked era in which the global economy,trade,personnel,and information are closely connected,studies on China’s global position and its status changes and influencing factors in multiple contact networks are still insufficient.In this study,from the perspective of diverse global contact networks,we constructed economic,cultural,and political influence indices to explore the changes and influencing factors on China’s status in the global system from 2005 to 2018.The results show that during the study period,China’s global influence in the fields of economic ties,cultural exchanges,and political contacts increased significantly,but its influ-ence in the fields of cultural exchanges and political contacts lagged far economic ties.The pattern of China’s economic influence on various economies around the world has shown a transformation from an‘upright pyramid’to an‘inverted pyramid’structure.The proportion of these economies in low-influence zones has decreased from more than 60%in 2005 to less than 20%in 2018.China’s cultural and political influence on various economies around the world has increased significantly;however,for the former,the percentage of high-influence areas is still less than 20%,whereas for the latter the percentage of these economies in medium-and high-influence areas is still less than 50%.Analyses such as a scatter plot matrix show that geographical proximity,economic globalization,close cooperation with developing countries,and a proactive and peaceful foreign policy are important factors in improving China’s status in the diverse global network system.
基金the National Natural Science Foundation of China(Grant No.42174047 and No.42174036)the National Science Foundation Project for Outstanding Youth(No.42104034).
文摘This paper realizes the full-domain collaborative deployment of multiple interference sources of the global satellite navigation system(GNSS)and evaluates the deployment effect to enhance the ability to disturb the attacker and the capability to defend the GNSS during navigation countermeasures.Key evaluation indicators for the jamming effect of GNSS suppressive and deceptive jamming sources are first created,their evaluation models are built,and their detection procedures are sorted out,as the basis for determining the deployment principles.The principles for collaboratively deploying multi-jamming sources are developed to obtain the deployment structures(including the required number,structures in demand,and corresponding positions)of three single interference sources required by collaboratively deploying.Accordingly,simulation and hardware-in-loop testing results are presented to determine a rational configuration of the collaborative deployment of multi-jamming sources in the set situation and further realize the full-domain deployment of an interference network from ground,air to space.Varied evaluation indices for the deployment effect are finally developed to evaluate the deployment effect of the proposed configuration and further verify its reliability and rationality.
基金supported by the National Natural Science Foundation of China(12371150,11971432)the Natural Science Foundation of Zhejiang Province(LY21G010003)+2 种基金the Management Project of"Digital+"Discipline Construction of Zhejiang Gongshang University(SZJ2022A012,SZJ2022B017)the Characteristic&Preponderant Discipline of Key Construction Universities in Zhejiang Province(Zhejiang Gongshang University-Statistics)the Scientific Research Projects of Universities in Anhui Province(2022AH050955)。
文摘Let X={X(t)∈R^(d),t∈R^(N)}be a centered space-time anisotropic Gaussian field with indices H=(H_(1),…,H_(N))∈(0,1)~N,where the components X_(i)(i=1,…,d)of X are independent,and the canonical metric√(E(X_(i)(t)-X_(i)(s))^(2))^(1/2)(i=1,…,d)is commensurate with■for s=(s_(1),…,s_(N)),t=(t_(1),…,t_(N))∈R~N,α_(i)∈(0,1],and with the continuous functionγ(·)satisfying certain conditions.First,the upper and lower bounds of the hitting probabilities of X can be derived from the corresponding generalized Hausdorff measure and capacity,which are based on the kernel functions depending explicitly onγ(·).Furthermore,the multiple intersections of the sample paths of two independent centered space-time anisotropic Gaussian fields with different distributions are considered.Our results extend the corresponding results for anisotropic Gaussian fields to a large class of space-time anisotropic Gaussian fields.
基金funded by the National Key R&D Program of China[2021YFC2301102]National Natural Science Foundation of China[82202593]Key R&D Program of Hebei Province[223777100D].
文摘Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP.Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays.Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05).Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.
基金supported by the State Key Laboratory of Technology and Equipment for Defense against Power System Operational Risks(No.SGNR0000KJJS2302137)the National Natural Science Foundation of China(Grant No.62203248)the Natural Science Foundation of Shandong Province(Grant No.ZR2020ME194).
文摘High-voltage circuit breakers are the core equipment in power networks,and to a certain extent,are related to the safe and reliable operation of power systems.However,their core components are prone to mechanical faults.This study proposes a component separation method to detect multiple mechanical faults in circuit breakers that can achieve online real-time monitoring.First,a model and strategy are presented for obtaining mechanical voiceprint signals from circuit breakers.Subsequently,the component separation method was used to decompose the voiceprint signals of multiple faults into individual component signals.Based on this,the recognition of the features of a single-fault voiceprint signal can be achieved.Finally,multiple faults in high-voltage circuit breakers were identified through an experimental simulation and verification of the circuit breaker voiceprint signals collected from the substation site.The research results indicate that the proposed method exhibits excellent performance for multiple mechanical faults,such as spring structures and loose internal components of circuit breakers.In addition,it provides a reference method for the real-time online monitoring of high-voltage circuit breakers.
基金primarily supported by the Chinese National Natural Science Foundation of China(Grant No. G42192553)Open Fund of Fujian Key Laboratory ofSevere Weather and Key Laboratory of Straits Severe Weather(Grant No. 2023KFKT03)+6 种基金the Open Project Fund of China Meteorological Administration Basin Heavy Rainfall Key Laboratory(Grant No. 2023BHR-Y20)the Open Fund of the State Key Laboratory of Remote Sensing Science (Grant No. OFSLRSS202321)the Program of Shanghai Academic/Technology Research Leader(Grant No. 21XD1404500)the Shanghai Typhoon Research Foundation (Grant No. TFJJ202107)the Chinese National Natural Science Foundation of China (Grant No. G41805016)the National Meteorological Center Foundation (Grant No. FY-APP-2021.0207)the High Performance Computing Center of Nanjing University of Information Science&Technology for their support of this work
文摘This paper presents an attempt at assimilating clear-sky FY-4A Advanced Geosynchronous Radiation Imager(AGRI)radiances from two water vapor channels for the prediction of three landfalling typhoon events over the West Pacific Ocean using the 3DVar data assimilation(DA)method along with the WRF model.A channel-sensitive cloud detection scheme based on the particle filter(PF)algorithm is developed and examined against a cloud detection scheme using the multivariate and minimum residual(MMR)algorithm and another traditional cloud mask–dependent cloud detection scheme.Results show that both channel-sensitive cloud detection schemes are effective,while the PF scheme is able to reserve more pixels than the MMR scheme for the same channel.In general,the added value of AGRI radiances is confirmed when comparing with the control experiment without AGRI radiances.Moreover,it is found that the analysis fields of the PF experiment are mostly improved in terms of better depicting the typhoon,including the temperature,moisture,and dynamical conditions.The typhoon track forecast skill is improved with AGRI radiance DA,which could be explained by better simulating the upper trough.The impact of assimilating AGRI radiances on typhoon intensity forecasts is small.On the other hand,improved rainfall forecasts from AGRI DA experiments are found along with reduced errors for both the thermodynamic and moisture fields,albeit the improvements are limited.
基金National Natural Science Foundation of China(Grant Nos.11972193 and 92266201)。
文摘How to effectively evaluate the firing precision of weapon equipment at low cost is one of the core contents of improving the test level of weapon system.A new method to evaluate the firing precision of the MLRS considering the credibility of simulation system based on Bayesian theory is proposed in this paper.First of all,a comprehensive index system for the credibility of the simulation system of the firing precision of the MLRS is constructed combined with the group analytic hierarchy process.A modified method for determining the comprehensive weight of the index is established to improve the rationality of the index weight coefficients.The Bayesian posterior estimation formula of firing precision considering prior information is derived in the form of mixed prior distribution,and the rationality of prior information used in estimation model is discussed quantitatively.With the simulation tests,the different evaluation methods are compared to validate the effectiveness of the proposed method.Finally,the experimental results show that the effectiveness of estimation method for firing precision is improved by more than 25%.
基金Project supported by the Heilongjiang Province Natural Science Foundation Joint Guidance Project,China (Grant No.LH2020F022)the Fundamental Research Funds for the Central Universities,China (Grant No.3072022CF0801)。
文摘Conservative chaotic systems have unique advantages over dissipative chaotic systems in the fields of secure communication and pseudo-random number generator because they do not have attractors but possess good traversal and pseudorandomness. In this work, a novel five-dimensional(5D) Hamiltonian conservative hyperchaotic system is proposed based on the 5D Euler equation. The proposed system can have different types of coordinate transformations and time reversal symmetries. In this work, Hamilton energy and Casimir energy are analyzed firstly, and it is proved that the new system satisfies Hamilton energy conservation and can generate chaos. Then, the complex dynamic characteristics of the system are demonstrated and the conservatism and chaos characteristics of the system are verified through the correlation analysis methods such as phase diagram, equilibrium point, Lyapunov exponent, bifurcation diagram, and SE complexity. In addition, a detailed analysis of the multistable characteristics of the system reveals that many energy-related coexisting orbits exist. Based on the infinite number of center-type and saddle-type equilibrium points, the dynamic characteristics of the hidden multistability of the system are revealed. Then, the National Institute of Standards and Technology(NIST)test of the new system shows that the chaotic sequence generated by the system has strong pseudo-random. Finally, the circuit simulation and hardware circuit experiment of the system are carried out with Multisim simulation software and digital signal processor(DSP) respectively. The experimental results confirm that the new system has good ergodicity and realizability.
基金This study is supported by the National Key Research and Development Program of China(2017YFB0307500).
文摘Implementing a new energy-saving electrochemical synthesis system with high commercial value is a strategy of the sustainable development for upgrading the bulk chemicals preparation technology in the future.Here,we report a multiple redox-mediated linear paired electrolysis system,combining the hydrogen peroxide mediated cathode process with the I2 mediated anode process,and realize the conversion of furfural to furoic acid in both side of the dividedflow cell simultaneously.By reasonably controlling the cathode potential,the undesired water splitting reaction and furfural reduction side reactions are avoided.Under the galvanostatic electrolysis,the two-mediated electrode processes have good compatibility,which reduce the energy consumption by about 22%while improving the electronic efficiency by about 125%.This system provides a green electrochemical synthesis route with commercial prospects.
基金supported by the National Natural Science Foundation of China(Nos.11875274 and U1232202)。
文摘In the research and development of new silicon pixel detectors,a collimated monoenergetic charged-particle test beam equipped with a high-resolution pixel-beam telescope is crucial for prototype verification and performance evaluation.When the beam energy is low,the effect of multiple Coulomb scattering on the measured resolution of the Device Under Test(DUT)must be considered to accurately evaluate the performance of the pixel chips and detectors.This study aimed to investigate the effect of multiple Coulomb scattering on the measured resolution,particularly at low beam energies.Simulations were conducted using Allpix^(2) to study the effects of multiple Coulomb scattering under different beam energies,material budgets,and telescope layouts.The simulations also provided the minimum energy at which the effect of multiple Coulomb scattering could be ignored.Compared with the results of a five-layer detector system tested with an electron beam at DESY,the simulation results were consistent with the beam test results,confirming the reliability of the simulations.
基金supported by Incubation Program for Clinical Trials(No.19HXFH030)Achievement Transformation Project(No.CGZH21001)+4 种基金1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21007)Translational Research Grant of NCRCH(No.2021WWB03),Chengdu Science and Technology Program(No.2022-YF05-01444-SN)Key Research and Development Program of Sichuan Province(No.2023YFS0031)Post-Doctor Research Project,West China Hospital,Sichuan University(No.2023HXBH111)National Key Research and Development Program of China(Nos.2022YFC2502600,2022YFC2502603).
文摘Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.
基金supported by the“GZ Hematologic Malignancy MARKER GHROMOS of Education Department of Liaoning Province”Grant(Grant Number:07102).
文摘Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response varies among individuals.Genetic factor may play an important role in BIPN.Methods:A nextgeneration sequencing(NGS)panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy.mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR(RT-qPCR).Serum homocysteine(Hcy)levels were detected in 40 samples by chemiluminescent microparticle immunoassay(CMIA).Results:Compared with the non-BIPN group(n=89),a total of 8 significantly associated single nucleotide polymorphisms(SNPs)were identified in the BIPN group(n=115):MTHFR(rs1801131,rs1801133,rs17421511),EPHX1(rs1051740),MME(rs2016848),ALDH1A1(rs6151031),HTR7(rs1935349)and CYP2A6(rs8192720).The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment(NP group)was lower than that of newly diagnosed patients without peripheral neuritis after treatment(NnP group)(1.70±0.77 vs.2.81±0.97,p=0.009).Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group(11.66±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/L,p≤0.001).Conclusion:CYP2A6,EPHX1,MTHFR,ALDH1A1,HTR7,MME and BIPN are linked in Chinese MM patients.BIPN is more likely to occur in patients with lower MTHFR mRNA expression,which might result in higher serum Hcy levels.