Environmental Conditions Conducive to the Formation of Multiple Tropical Cyclones over the Western North Pacific

There is limited understanding regarding the formation of multiple tropical cyclones(MTCs).This study explores the environmental conditions conducive to MTC formation by objectively determining the atmospheric circulation patterns favorable for MTC formation over the western North Pacific.Based on 199 MTC events occurring from June to October 1980–2020,four distinct circulation patterns are identified:the monsoon trough(MT)pattern,accounting for 40.3%of occurrences,the confluence zone(CON)pattern at 26.2%,the easterly wave(EW)pattern at 17.8%,and the monsoon gyre(MG)pattern at 15.7%.The MT pattern mainly arises from the interaction between the subtropical high and the monsoon trough,with MTCs forming along the monsoon trough and its flanks.The CON pattern is affected by the subtropical high,the South Asian high,and the monsoon trough,with MTCs emerging at the confluence zone where the prevailing southwesterly and southeasterly flows converge.The EW pattern is dominated by easterly flows,with MTCs developing along the easterly wave train.MTCs in the MG pattern arise within a monsoon vortex characterized by strong southwesterly flows.A quantitative analysis further indicates that MTC formation in the MT pattern is primarily governed by mid-level vertical velocity and low-level vorticity,while mid-level humidity and vertical velocity are significantly important in the other patterns.The meridional shear and convergence of zonal winds are essential in converting barotropic energy from the basic flows to disturbance kinetic energy,acting as the primary source for eddy kinetic energy growth.

Multiple pulp stones emerge across all teeth during mixed dentition:A case report

BACKGROUND This paper reports a rare presentation of multiple pulp stones(PSs)emerging in all teeth during mixed dentition.It offers valuable insights into the clinical diagnosis,treatment,and prognosis of multiple PSs,shedding light on their occurrence during the mixed dentition period.CASE SUMMARY A 10-year-old girl presented with repeated pain in the mandibular right posterior teeth.Intraoral examination revealed carious lesions,abnormal tooth shapes,and anomalies in tooth number.Radiographic examinations showed multiple PSs with diverse shapes,sizes,and quantities in all teeth,alongside anomalies in tooth shape and number.Root canal therapy was initiated,but the patient initially lacked timely follow-up.Upon return for treatment completion,an extracted tooth revealed irregular calculus within the pulp cavity.CONCLUSION This case underscores the importance of considering multiple PSs in mixed dentition,necessitating comprehensive evaluation and management strategies.

A Review on Vibration Control of Multiple Cylinders Subjected to FlowInduced Vibrations

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.

In situ formation of multiple catalysts for enhancing the hydrogen storage of MgH_(2) by adding porous Ni_(3)ZnC_(0.7)/Ni loaded carbon nanotubes microspheres

MgH_(2) is considered one of the most promising hydrogen storage materials because of its safety,high efficiency,high hydrogen storage quantity and low cost characteristics.But some shortcomings are still existed:high operating temperature and poor hydrogen absorption dynamics,which limit its application.Porous Ni_(3)ZnC_(0.7)/Ni loaded carbon nanotubes microspheres(NZC/Ni@CNT)is prepared by facile filtration and calcination method.Then the different amount of NZC/Ni@CNT(2.5,5.0 and 7.5 wt%)is added to the MgH_(2) by ball milling.Among the three samples with different amount of NZC/Ni@CNT(2.5,5.0 and 7.5 wt%),the MgH_(2)-5 wt%NZC/Ni@CNT composite exhibits the best hydrogen storage performances.After testing,the MgH_(2)-5 wt%NZC/Ni@CNT begins to release hydrogen at around 110℃ and hydrogen absorption capacity reaches 2.34 wt%H_(2) at 80℃ within 60 min.Moreover,the composite can release about 5.36 wt%H_(2) at 300℃.In addition,hydrogen absorption and desorption activation energies of the MgH_(2)-5 wt%NZC/Ni@CNT composite are reduced to 37.28 and 84.22 KJ/mol H_(2),respectively.The in situ generated Mg_(2)NiH_(4)/Mg_(2)Ni can serve as a"hydrogen pump"that plays the main role in providing more activation sites and hydrogen diffusion channels which promotes H_(2) dissociation during hydrogen absorption process.In addition,the evenly dispersed Zn and MgZn2 in Mg and MgH_(2) could provide sites for Mg/MgH_(2) nucleation and hydrogen diffusion channel.This attempt clearly proved that the bimetallic carbide Ni_(3)ZnC_(0.7) is a effective additive for the hydrogen storage performances modification of MgH_(2),and the facile synthesis of the Ni_(3)ZnC_(0.7)/Ni@CNT can provide directions of better designing high performance carbide catalysts for improving MgH_(2).

Multiple factors influencing high-purity indium electrolytic refining

The effects of various contaminants in the electrolytic refinement of indium were investigated using a glow discharge mass spectrometer(GDMS).The effects of several factors such as the indium ion(In3+)concentration,the sodium chloride(NaCl)concentration,the current density,the gelatin concentration,the pH,and the electrode distance,were examined.Significant variations in impurity levels concerning gelatin concentration were observed.Both the gelatin and In3+concentration were moderately positively correlated with the Pb content.The Sb concentration was associated positively with the NaCl concentration,while the Ti concentration had an adverse correlation with the NaCl concentration.The Bi element content was positively linked to the electrode distance.As the current density increased,Cu,Pb,and Bi impurities initially rose and then eventually declined.Notably,a critical current density of 45 A·m^(-2) was identified in this behavior.

A"messenger zone hypothesis"based on the visual three-dimensional spatial distribution of motoneurons innervating deep limb muscles

Coordinated contraction of skeletal muscles relies on selective connections between the muscles and multiple classes of the spinal motoneuro ns.Howeve r,current research on the spatial location of the spinal motoneurons innervating differe nt muscles is limited.In this study,we investigated the spatial distribution and relative position of different motoneurons that control the deep muscles of the mouse hindlimbs,which were innervated by the obturator nerve,femoral nerve,inferior gluteal nerve,deep pe roneal nerve,and tibial nerve.Locations were visualized by combining a multiplex retrograde tracking technique compatible with three-dimensional imaging of solvent-cleared o rgans(3DISCO)and 3-D imaging technology based on lightsheet fluorescence microscopy(LSFM).Additionally,we propose the hypothesis that"messenger zones"exist as interlaced areas between the motoneuron pools that dominate the synergistic or antagonist muscle groups.We hypothesize that these interlaced neurons may participate in muscle coordination as messenger neurons.Analysis revealed the precise mutual positional relationships among the many motoneurons that innervate different deep muscles of the mouse.Not only do these findings update and supplement our knowledge regarding the overall spatial layout of spinal motoneurons that control mouse limb muscles,but they also provide insights into the mechanisms through which muscle activity is coordinated and the architecture of motor circuits.

Multiple myeloma survival in New South Wales, Australia, by treatment era to 2020

Objective: Australia has relatively high multiple myeloma(MM) incidence and mortality rates. Advancements in MM treatment over recent decades have driven improvements in MM survival in high-income countries;however, reporting in Australia is limited. We investigated temporal trends in population-wide MM survival across 3 periods of treatment advancements in New South Wales(NSW), Australia.Methods: Individuals with an MM diagnosis in the NSW Cancer Registry between 1985 and 2015 with vital follow-up to 2020, were categorized into 3 previously defined treatment eras according to their diagnosis date(1985±1995, chemotherapy only;1996±2007, autologous stem cell transplantation;and 2008±2015, novel agents including proteasome inhibitors and immunomodulatory drugs). Both relative survival and cause-specific survival according to Fine and Gray's competing risks cumulative incidence function were calculated by treatment era and age at diagnosis.Results: Overall, 11,591 individuals were included in the study, with a median age of 70 years at diagnosis. Five-year relative survival improved over the 36-year(1985±2020) study period(31.0% in 1985±1995;41.9% in 1996±2007;and 56.1% in 2008±2015). For individuals diagnosed before 70 years of age, the 5-year relative survival nearly doubled, from 36.5% in 1985±1995 to 68.5% in 2008±2015. Improvements for those > 70 years of age were less pronounced between 1985±1995 and 1996±2007;however, significant improvements were observed for those diagnosed in 2008±2015. Similar overall and age-specific patterns were observed for causespecific survival. After adjustment for gender and age at diagnosis, treatment era was strongly associated with both relative and cause-specific survival(P < 0.0001).Conclusions: Survival of individuals with MM is improving in Australia with treatment advances. However, older age groups continue to experience poor survival outcomes with only modest improvements over time. Given the increasing prevalence of MM in Australia, the effects of MM treatment on quality of life, particularly in older age, warrant further attention.

Changes of China’s Status in the Global System and Its Influencing Factors:A Multiple Contact Networks Perspective

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.

Characteristic analysis of 5D symmetric Hamiltonian conservative hyperchaotic system with hidden multiple stability

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.

Linear paired electrolysis of furfural to furoic acid at both anode and cathode in a multiple redox mediated system

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.

Effect of multiple coulomb scattering on the beam tests of silicon pixel detectors

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.

Development of a cell adhesion-based prognostic model for multiple myeloma:Insights into chemotherapy response and potential reversal of adhesion effects

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.

Improving early diagnosis of multiple endocrine neoplasia type 1 by assessing the gastrointestinal symptoms,hypercalcemia,and elevated serum gastrin

Despite advancements in the field,early diagnosis of multiple endocrine neoplasia type 1(MEN1)remains unachievable.This letter to the editor highlighted the importance of carefully assessing gastrointestinal symptoms,hypercalcemia,and elevated serum gastrin levels,as suggested by Yuan et al in their paper.They focused on a patient with recurrent abdominal pain and diarrhea whose diagnostic path led to establishing a MEN1 diagnosis within a year.This emphasized the need for clinicians to consider MEN1 in patients with similar presentations,particularly when gastrointestinal symptoms persist or recur after discontinuation of proton pump inhibitors,especially knowing that early recognition and intervention are crucial for improving patient outcomes.

Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

MULTIPLE SOLUTIONS TO CRITICAL MAGNETIC SCHRODINGER EQUATIONS

In this paper,we are concerned with the existence of multiple solutions to the critical magnetic Schrödinger equation(-i▽-a(x))^(2)u+⒂λV(x)u=p|u|^(p-2)u+(∫R(n)|u(y)|^(2)_(a)^(*)/|x-y|^(a)dy)|u|2_(a)^(*)-2_(u)in R^(N),(0.1)where N≥4,2≤p<2^(*),2_α^(*)=(2N-α)/(N-2)with 0<α<4,λ>0,μ∈R,A(x)=(A_(1)(x),A_(2)(x),…,A_(N)(x))is a real local Hölder continuous vector function,i is the imaginary unit,and V(x)is a real valued potential function on R^(N).Supposing thatΩ=int V^(-1)(0)■R^(N)is bounded,we show that problem(0.1)possesses at least cat_(Ω)(Ω)nontrivial solutions ifλis large.

Systemic lupus erythematosus in a 15-year-old female with multiple splenic nodules:A case report

BACKGROUND Systemic lupus erythematosus(SLE)is a chronic inflammatory disease primarily affecting young females.SLE can invade any organ,and various forms of splenic invasion have been reported.Manifestations include splenomegaly and splenic infarction,rupture,and calcification.The study encountered a rare case of splenic involvement,with nodules of various sizes without calcifications or ruptures.CASE SUMMARY A 15-year-old girl presented with arthralgia,weight loss,fever,increased levels of inflammatory markers,and positive antinuclear antibody test results.The patient was diagnosed with SLE.She was asymptomatic while taking steroids and hydroxychloroquine.Ten months after discharge,the patient developed a fever and abdominal pain.Lupus enteritis was suspected,and abdominopelvic computed tomography(AP-CT)was performed.There were no specific findings in the gastrointestinal tract,but multiple splenic nodules were observed.Infection or hemangioma was considered;however,no specific radiological findings were observed.A biopsy of the spleen was performed to determine the possibility of malignancy.The histological findings of the spleen included extensive periarteriolar necrosis with hematoxylin bodies and numerous karyorrhectic debris.Based on the biopsy results,the patient was diagnosed with an SLE flare-up and was maintained on high-dose steroids and immunosuppressants.CONCLUSION As disease activity increased,multiple nodules in the spleen that were previously unseen were observed using AP-CT and histologically confirmed.Spleen invasion by SLE can appear in multiple nodular forms and patterns.Therefore,physicians should consider these findings when differentiating these nodules from infections and malignancies.

Plasmacytosis mimicking multiple myeloma in angioimmunoblastic T-cell lymphoma:A case report and review of literature

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL)is a common subtype of peripheral T-cell lymphoma.Approximately half of patients with AITL may concurrently present with hypergammaglobulinemia.Increased numbers of plasma cells in the bone marrow are commonly observed at diagnosis.These tumors mimic plasma cell myelomas,hindering a conundrum of clinical diagnoses and potentially delaying appropriate treatment.CASE SUMMARY A 78-year-old woman experienced poor appetite,weight loss of 5 kg,fatigue 2 months before presentation,and shortness of breath 2 d before presentation,but no fever or night sweats.Physical examination revealed splenomegaly and many palpable masses over the bilateral axillary regions,approximately>2 cm in size,with rubbery consistency and no tenderness.Blood tests revealed anemia and thrombocytopenia,lactate dehydrogenase level of 153 U/L,total protein level of 10.9 g/dL,albumin to globulin ratio of 0.2,and immunoglobulin G level more than the upper limit of 3000 mg/dL.The free kappa and lambda light chain concentrations were 451 and 614 mg/L,respectively.A pathological examination confirmed the diagnosis of AITL.The initial treatment was the cyclophosphamide,epirubicin,vincristine,and prednisolone regimen.Following this treatment,pleural effusion was controlled,and the patient was discharged in a stable condition and followed up in our outpatient department.CONCLUSION This report highlights the importance of differentiating reactive plasmacytosis from plasma cell myeloma in patients with hypergammaglobulinemia.A precise diagnosis of AITL requires a comprehensive evaluation,involving clinical,immunophenotypic,and histological findings conducted by a multidisciplinary team to ensure appropriate treatment.

Scarcity and Mental Health—Multiple Mediators of Sleep Quality and Life Satisfaction

Background:In the current social environment,scarcity,as a universally present objective state,profoundly impacts individuals’decision-making and health through the subjective feeling it induces,known as a“scarcity mindset.”Particularly,the feeling of scarcity related to money and sleep time is not only widespread but also directly linked to an individual’s mental health.Purpose:This study aims to delve into the relationship between the feeling of scarcity and mental health,with a specific focus on the relationship between the feeling of money scarcity or sleep time scarcity and mental health,as well as the role of sleep quality or life satisfaction in this relationship.Procedure:We determined the sampling quotas based on the population and economic development levels of each province in the“China Statistical Yearbook(2021)”(National Bureau of Statistics,2021).Participants were selected using the Probability Proportional to Size(PPS)sampling method.Data was collected by distributing online questionnaires to participants,and the relationships between the main variables were explored using structural equation modeling.Results:1.In China,the feeling of sleep time scarcity is stronger than the feeling of money scarcity among the public.2.The feeling of money scarcity is positively correlated with depression and anxiety,whereas the feeling of sleep time scarcity is only positively correlated with depression.3.The feeling of scarcity mainly leads to depression and self-denial through reducing life satisfaction,and it leads to anxiety through reducing sleep quality.Conclusion:The feeling of scarcity in money and sleep time is related to different dimensions of mental health.Therefore,reasonably planning financial allocation and ensuring an adequate amount of sleep can reduce the sense of scarcity,thereby improving mental health.Additionally,improving sleep quality and increasing life satisfaction can alleviate the adverse effects of scarcity on mental health.

Gene signatures to therapeutics:Assessing the potential of ivermectin against t(4;14)multiple myeloma

BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.

Treatment Efficacy and Safety of Bortezomib Combined with Dexamethasone and Lenalidomide Chemotherapy Regimen for Multiple Myeloma

Objective:To analyze the effect of bortezomib combined with dexamethasone and lenalidomide in the treatment of multiple myeloma.Methods:60 cases of multiple myeloma patients admitted to our hospital from January 2022 to December 2023 were selected randomly,with 30 cases in each group.Bortezomib combined with dexamethasone was administered in the control group,and bortezomib combined with dexamethasone and lenalidomide was given to the observation group,and the treatment effect was analyzed.Results:After treatment,CD^(3+)and CD^(4+)of the observation group were higher than that of the control group,CD^(8+)was lower than that of the control group,and the total treatment efficiency was higher,which was statistically significant(P<0.05),and there was no difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion:Bortezomib combined with dexamethasone and lenalidomide is effective in the treatment of multiple myeloma as it regulates the immune function and is safe,thus it can be promoted in clinical practice.