Joint time–frequency analysis is an emerging method for interpreting the underlying physics in fuel cells,batteries,and supercapacitors.To increase the reliability of time–frequency analysis,a theoretical correlatio...Joint time–frequency analysis is an emerging method for interpreting the underlying physics in fuel cells,batteries,and supercapacitors.To increase the reliability of time–frequency analysis,a theoretical correlation between frequency-domain stationary analysis and time-domain transient analysis is urgently required.The present work formularizes a thorough model reduction of fractional impedance spectra for electrochemical energy devices involving not only the model reduction from fractional-order models to integer-order models and from high-to low-order RC circuits but also insight into the evolution of the characteristic time constants during the whole reduction process.The following work has been carried out:(i)the model-reduction theory is addressed for typical Warburg elements and RC circuits based on the continued fraction expansion theory and the response error minimization technique,respectively;(ii)the order effect on the model reduction of typical Warburg elements is quantitatively evaluated by time–frequency analysis;(iii)the results of time–frequency analysis are confirmed to be useful to determine the reduction order in terms of the kinetic information needed to be captured;and(iv)the results of time–frequency analysis are validated for the model reduction of fractional impedance spectra for lithium-ion batteries,supercapacitors,and solid oxide fuel cells.In turn,the numerical validation has demonstrated the powerful function of the joint time–frequency analysis.The thorough model reduction of fractional impedance spectra addressed in the present work not only clarifies the relationship between time-domain transient analysis and frequency-domain stationary analysis but also enhances the reliability of the joint time–frequency analysis for electrochemical energy devices.展开更多
BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing t...BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.展开更多
Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not ...Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.展开更多
Objective:This study used comprehensive bioinformatics analysis and network pharmacology analysis to investigate the potentially relevant mechanisms of Sophora flavescens against cervical squamous cell carcinoma.Metho...Objective:This study used comprehensive bioinformatics analysis and network pharmacology analysis to investigate the potentially relevant mechanisms of Sophora flavescens against cervical squamous cell carcinoma.Methods:Consistently altered genes involved in cervical squamous cell cancerization were analyzed in the GEO database.The chemical ingredients and target genes of Sophora flavescens were explored using the TCMSP database.We obtained the potential therapeutic targets of Sophora flavescens by intersecting the above genesets and validated them in the GEPIA database.The interaction between Sophora flavescens and target genes was predicted by molecular docking.RT-qPCR was used to verify the changes of target genes in HeLa cells treated with Sophora flavescens.Single-gene GSEA functional analysis were performed to determine the molecular mechanisms.Results:Fifteen genes related to the transformation of cervical squamous cell carcinoma were identified,among which AR and ESR1 were confirmed as targets for kaempferol,wighteone,formononetin,and phaseolinon.These compounds are the active ingredients in Sophora flavescens.Low expressions of AR and ESR1 correlate with a poor prognosis,while Sophora flavescens treatment increases the expression of AR and ESR1 in HeLa.GSEA analysis showed that AR and ESR1 mainly participate in the epithelial-mesenchymal transition in cervical squamous cell carcinoma.Conclusion:Sophora flavescens exert anti-tumor effects by targeting AR and ESR1,which may regulate cancer metastasis.展开更多
Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnosti...Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.展开更多
In the last two decades the study of red blood cell elasticity using optical tweezers has known a rise appearing in the scientific research with regard to the various works carried out. Despite the various work done, ...In the last two decades the study of red blood cell elasticity using optical tweezers has known a rise appearing in the scientific research with regard to the various works carried out. Despite the various work done, no study has been done so far to study the influence of friction on the red blood cell indentation response using optical tweezers. In this study, we have developed a new approach to determine the coefficient of friction as well as the frictional forces of the red blood cell. This approach therefore allowed us to simultaneously carry out the indentation and traction test, which allowed us to extract the interfacial properties of the microbead red blood cell couple, among other things, the friction coefficient. This property would be extremely important to investigate the survival and mechanical features of cells, which will be of great physiological and pathological significance. But taking into account the hypothesis of friction as defined by the isotropic Coulomb law. The experiment performed for this purpose is the Brinell Hardness Test (DB).展开更多
BACKGROUND:Emergency patients with sepsis or septic shock are at high risk of death.Despite increasing attention to microhemodynamics,the clinical use of advanced microcirculatory assessment is limited due to its shor...BACKGROUND:Emergency patients with sepsis or septic shock are at high risk of death.Despite increasing attention to microhemodynamics,the clinical use of advanced microcirculatory assessment is limited due to its shortcomings.Since blood gas analysis is a widely used technique reflecting global oxygen supply and consumption,it may serve as a surrogate for microcirculation monitoring in septic treatment.METHODS:We performed a search using PubMed,Web of Science,and Google scholar.The studies and reviews that were most relevant to septic microcirculatory dysfunctions and blood gas parameters were identified and included.RESULTS:Based on the pathophysiology of oxygen metabolism,the included articles provided a general overview of employing blood gas analysis and its derived set of indicators for microhemodynamic monitoring in septic care.Notwithstanding flaws,several parameters are linked to changes in the microcirculation.A comprehensive interpretation of blood gas parameters can be used in order to achieve hemodynamic optimization in septic patients.CONCLUSION:Blood gas analysis in combination with clinical performance is a reliable alternative for microcirculatory assessments.A deep understanding of oxygen metabolism in septic settings may help emergency physicians to better use blood gas analysis in the evaluation and treatment of sepsis and septic shock.展开更多
BACKGROUND Previous studies have reported that low hematocrit levels indicate poor survival in patients with ovarian cancer and cervical cancer,the prognostic value of hematocrit for colorectal cancer(CRC)patients has...BACKGROUND Previous studies have reported that low hematocrit levels indicate poor survival in patients with ovarian cancer and cervical cancer,the prognostic value of hematocrit for colorectal cancer(CRC)patients has not been determined.The prognostic value of red blood cell distribution width(RDW)for CRC patients was controversial.AIM To investigate the impact of RDW and hematocrit on the short-term outcomes and long-term prognosis of CRC patients who underwent radical surgery.METHODS Patients who were diagnosed with CRC and underwent radical CRC resection between January 2011 and January 2020 at a single clinical center were included.The short-term outcomes,overall survival(OS)and disease-free survival(DFS)were compared among the different groups.Cox analysis was also conducted to identify independent risk factors for OS and DFS.RESULTS There were 4258 CRC patients who underwent radical surgery included in our study.A total of 1573 patients were in the lower RDW group and 2685 patients were in the higher RDW group.There were 2166 and 2092 patients in the higher hematocrit group and lower hematocrit group,respectively.Patients in the higher RDW group had more intraoperative blood loss(P<0.01)and more overall complications(P<0.01)than did those in the lower RDW group.Similarly,patients in the lower hematocrit group had more intraoperative blood loss(P=0.012),longer hospital stay(P=0.016)and overall complications(P<0.01)than did those in the higher hematocrit group.The higher RDW group had a worse OS and DFS than did the lower RDW group for tumor node metastasis(TNM)stage I(OS,P<0.05;DFS,P=0.001)and stage II(OS,P=0.004;DFS,P=0.01)than the lower RDW group;the lower hematocrit group had worse OS and DFS for TNM stage II(OS,P<0.05;DFS,P=0.001)and stage III(OS,P=0.001;DFS,P=0.001)than did the higher hematocrit group.Preoperative hematocrit was an independent risk factor for OS[P=0.017,hazard ratio(HR)=1.256,95%confidence interval(CI):1.041-1.515]and DFS(P=0.035,HR=1.194,95%CI:1.013-1.408).CONCLUSION A higher preoperative RDW and lower hematocrit were associated with more postoperative complications.However,only hematocrit was an independent risk factor for OS and DFS in CRC patients who underwent radical surgery,while RDW was not.展开更多
The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for sol...The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits.However,recent studies have shown that lymphatic endothelial cells(LECs)and blood endothelial cells(BECs)also play multifaceted roles in the tumor microenvironment beyond their structural functions,particularly in hepatocellular carcinoma(HCC).This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC,including their involvement in angiogenesis,immune modulation,lymphangiogenesis,and metastasis.By providing a detailed account of the complex interplay between LECs,BECs,and tumor cells,this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.展开更多
BACKGROUND Accumulating clinical evidence has shown that diabetes mellitus(DM)is a serious risk factor for cardiovascular disorders and an important factor for adverse cardiovascular events.AIM To explore the value of...BACKGROUND Accumulating clinical evidence has shown that diabetes mellitus(DM)is a serious risk factor for cardiovascular disorders and an important factor for adverse cardiovascular events.AIM To explore the value of the combined determination of the neutrophil-lymphocyte ratio(NLR)and red blood cell distribution width(RDW)in the early diagnosis and prognosis evaluation of DM complicated with heart failure(HF).METHODS We retrospectively analyzed clinical data on 65 patients with type 2 DM(T2DM)complicated with HF(research group,Res)and 60 concurrent patients with uncomplicated T2DM(control group,Con)diagnosed at Zhejiang Provincial People’s Hospital between January 2019 and December 2021.The NLR and RDW values were determined and comparatively analyzed,and their levels in T2DM+HF patients with different cardiac function grades were recorded.The receiver operating characteristic(ROC)curves were plotted to determine the NLR and RDW values(alone and in combination)for the early diagnosis of HF.The correlation between NLR and RDW with the presence or absence of cardiac events was also investigated.RESULTS Higher NLR and RDW levels were identified in the Res vs the Con groups(P<0.05).The NLR and RDW increased gradually and synchronously with the deterioration of cardiac function in the Res group,with marked differences in their levels among patients with grade II,III,and IV HF(P<0.05).ROC curve analysis revealed that NLR combined with RDW detection had an area under the curve of 0.915,a sensitivity of 76.9%,and a specificity of 100%for the early diagnosis of HF.Furthermore,HF patients with cardiac events showed higher NLR and RDW values compared with HF patients without cardiac events.CONCLUSION NLR and RDW were useful laboratory indicators for the early diagnosis of DM complicated with HF,and their joint detection was beneficial for improving diagnostic efficiency.Additionally,NLR and RDW values were directly proportional to patient outcomes.展开更多
In this work,we developed a simple and direct circuit model with a dual two-diode model that can be solved by a SPICE numerical simulation to comprehensively describe the monolithic perovskite/crystalline silicon(PVS/...In this work,we developed a simple and direct circuit model with a dual two-diode model that can be solved by a SPICE numerical simulation to comprehensively describe the monolithic perovskite/crystalline silicon(PVS/c-Si)tandem solar cells.We are able to reveal the effects of different efficiency-loss mechanisms based on the illuminated current density-voltage(J-V),semi-log dark J-V,and local ideality factor(m-V)curves.The effects of the individual efficiency-loss mechanism on the tandem cell’s efficiency are discussed,including the exp(V/VT)and exp(V/2VT)recombination,the whole cell’s and subcell’s shunts,and the Ohmic-contact or Schottky-contact of the intermediate junction.We can also fit a practical J-V curve and find a specific group of parameters by the trial-and-error method.Although the fitted parameters are not a unique solution,they are valuable clues for identifying the efficiency loss with the aid of the cell’s structure and experimental processes.This method can also serve as an open platform for analyzing other tandem solar cells by substituting the corresponding circuit models.In summary,we developed a simple and effective methodology to diagnose the efficiency-loss source of a monolithic PVS/c-Si tandem cell,which is helpful to researchers who wish to adopt the proper approaches to improve their solar cells.展开更多
Alloantibodies that are non ABO Alloimmunization to protein antigens happens only after exposure, in contrast to ABO isohaemagglutinins, which are present naturally, even in the absence of prior exposure. It is recogn...Alloantibodies that are non ABO Alloimmunization to protein antigens happens only after exposure, in contrast to ABO isohaemagglutinins, which are present naturally, even in the absence of prior exposure. It is recognized that while non-ABO RBC antibodies are less common than ABO antibodies, they generate essentially the same issues that lead to unfavorable clinical results. If non-ABO alloantibodies are identified early on, these issues related complications may be avoided This call for an in-depth understanding of the recipient and donor’s ABO-Rh grouping, antibody screening, and the phenotype of certain antigens. Equally important, the temporal association time between transplantation and hemolysis can help identify the underlying mechanism of hemolysis and direct appropriate management. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Finding the cause of post-HSCT anemia is essential for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia. In this case report review, we would like to highlight the vital role of transfusion medicine services and stem cell clinical teams in paying particular attention to the clinical significance of non-ABO alloantibodies involved to avoid causing overt hemolysis of incompatible donor RBCs or delayed erythropoiesis. Considering the fact that some of the Haematopoietic stem cell transplant centers do not give an attention to the other non-ABO RBC antigens.展开更多
Background:The cyclin-dependent kinase inhibitor 2a(CDKN2A)gene,identified as the multiple tumor suppressor gene,functions as a regulatory gene implicated in cancer pathogenesis.Its significance lies in its pivotal in...Background:The cyclin-dependent kinase inhibitor 2a(CDKN2A)gene,identified as the multiple tumor suppressor gene,functions as a regulatory gene implicated in cancer pathogenesis.Its significance lies in its pivotal involvement in the genesis of various tumors;notwithstanding,the precise connection between CDKN2A and c olon adenocarcinoma(COAD)remains undisclosed.Methods:The objective of this research was to assess the predictive importance of CDKN2A in COAD by analyzing data from The Cancer Genome Atlas database.Logistic regression,signed rank test,Wilcoxon test,and Kruskal-Wallis test were used to examine CDKN2A expression levels and clinicopathological features.Univariate and multivariate Cox r egression analyses and Kaplan-Meier analysis found prognostic variables.Additionally,gene set enrichment analysis identified key CDKN2A expression pathways.The study additionally examined CDKN2A expression with tumor immune infiltration using The Cancer Genome Atlas data and single sample gene set enrichment analysis.Results:The results of this investigation indicated a substantial connection between higher CDKN2A expression and negative outcomes in terms of overall survival and disease-related survival among COAD patients.Gene set enrichment analysis indicated a tight link between CDKN2A and both the cell cycle and hedgehog signaling pathways.Subsequent evaluation employing single sample gene set enrichment analysis demonstrated a positive link between CDKN2A expression with infiltration by iDCs,whereas a negative correlation was detected with infiltration by helper T cells.Conclusion:In conclusion,the present study gives strong data supporting the predictive value of CDKN2A and its possible usefulness as a biomarker for COAD.Additionally,our results show a reasonable link between CDKN2A expression and immune influx in COAD,putting light on the role of CDKN2A in the control of the tumor microenvironment.Nevertheless,additional studies are needed to confirm the underlying mechanisms of these relationships and to discover the therapeutic possibilities of targeting CDKN2A in the treatment of COAD.展开更多
Increasing evidence has shown that cell populations are not homogeneous,but rather heterogeneous,even within very small cell populations.Bulk measurements based on the homogenized cell population do not account for th...Increasing evidence has shown that cell populations are not homogeneous,but rather heterogeneous,even within very small cell populations.Bulk measurements based on the homogenized cell population do not account for the critical changes occurring in individual cells and are sometimes misleading.Cellular heterogeneity characteristics may be the key to address previously unsolved questions in disease development and progression.展开更多
Proton exchange membrane fuel cells(PEMFCs)are largely used in various applications because of their pollution-free products and high energy conversion efficiency.In order to improve the related design,in the present ...Proton exchange membrane fuel cells(PEMFCs)are largely used in various applications because of their pollution-free products and high energy conversion efficiency.In order to improve the related design,in the present work a new spiral flow field with a bypass is proposed.The reaction gas enters the flow field in the central path and diffuses in two directions through the flow channel and the bypass.The bypasses are arranged incrementally.The number of bypasses and the cross-section size of the bypasses are varied parametrically while a single-cell model of the PEMFC is used.The influence of the concentration of liquid water and oxygen in the cell on the performance of different flow fields is determined by means of Computational fluid dynamics(COMSOL Multiphysics software).Results show that when the bypass number is 48 and its cross-sectional area is 0.5 mm^(2),the cell exhibits the best performances.展开更多
The changes of CD4^+CD25^+ regulatory T cells (CD4^+CD25^+ Treg) and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma were investigated in order to elucidate the possible role...The changes of CD4^+CD25^+ regulatory T cells (CD4^+CD25^+ Treg) and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma were investigated in order to elucidate the possible roles of CD4^+CD25^+ Treg in the development of asthma. The peripheral blood samples were collected from 29 healthy controls (normal control group) and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD4^+CD25^+ Treg ratio and Foxp3 mRNA in PBMCs were detected. The CD4^+CD25^+ Treg ratio and Foxp3 mRNA in PBMCs of exacerbation and persistent groups were lower than that of remission and normal control groups (P〈0.05). Although the CD4^+CD25^+ Treg ratio and Foxp3 mRNA of remission group were also lower than that of normal control group, there was no significant difference between them (P〉0.05). As compared with persistent group, exacerbation group had lower CD4^+CD25^+ Treg ratio and Foxp3 mRNA (P〈0.05). It was indicated that the decrease of CD4^+CD25^+ Treg ratio and its function in PBMCs may be responsible for pathogenesis of asthma.展开更多
There is a small amount of clinical data regarding the safety and feasibility of autologous peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclero...There is a small amount of clinical data regarding the safety and feasibility of autologous peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis.The objectives of this retrospective study were to assess the safety and efficacy of peripheral blood mononuclear cell transplantation in 14 amyotrophic lateral sclerosis patients to provide more objective data for future clinical trials.After stem cell mobilization and collection,autologous peripheral blood mononuclear cells(1 × 109) were isolated and directly transplanted into the subarachnoid space of amyotrophic lateral sclerosis patients.The primary outcome measure was incidence of adverse events.Secondary outcome measures were electromyography 1 week before operation and 4 weeks after operation,Functional Independence Measurement,Berg Balance Scale,and Dysarthria Assessment Scale 1 week preoperatively and 1,2,4 and 12 weeks postoperatively.There was no immediate or delayed transplant-related cytotoxicity.The number of leukocytes,serum alanine aminotransferase and creatinine levels,and body temperature were within the normal ranges.Radiographic evaluation showed no serious transplant-related adverse events.Muscle strength grade,results of Functional Independence Measurement,Berg Balance Scale,and Dysarthria Assessment Scale were not significantly different before and after treatment.These findings suggest that peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis is safe,but its therapeutic effect is not remarkable.Thus,a large-sample investigation is needed to assess its efficacy further.展开更多
A novel method for determination of amino acids in individual human red blood cells has been developed. In this method, the derivatization reagents (NDA and CN-) are introduced into living cells by electroporation. ...A novel method for determination of amino acids in individual human red blood cells has been developed. In this method, the derivatization reagents (NDA and CN-) are introduced into living cells by electroporation. After completion of derivatization, the amino acids in a single cell is determined by capillary zone electrophoresis with end-column amperometric detection.展开更多
Hepatitis C virus(HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment ...Hepatitis C virus(HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment of dendritic cells(DCs) that play a central role in activating T cell responses. Although the impact of HCV on DC phenotype and function is likely to be more prominent in the liver, major HCV-induced alterations are detectable in peripheral blood DCs(pb DCs) that represent the most accessible source of DCs. These alterations include numerical reduction, impaired production of inflammatory cytokines and increased production of immunosuppressive IL10. These changes in DCs are relevant to our understanding the immune mechanisms underlying the propensity of HCV to establish persistent infection. Importantly, the noninvasive accessibility of pb DCs renders the analysis of these cells a convenient procedure that can be serially repeated in patient follow-up. Accordingly, the study of pb DCs in HCV-infected patients during conventional treatment with pegylated interferon and ribavirin indicated that restoration of normal plasmacytoid DC count may represent an additional mechanism contributing to the efficacy of the dual therapy. It also identified the pre-treatment levels of plasmacytoid DCs and IL10 as putative predictors of response to therapy. Treatment of chronic HCV infection is changing, as new generation direct-acting antiviral agents will soon be available for use in interferon-free therapeutic strategies. The phenotypic and functional analysis of pb DCs in this novel therapeutic setting will provide a valuable tool for investigating mechanisms underlying treatment efficacy and for identifying predictors of treatment response.展开更多
Clinical assessment of fluid volume status in children during malaria can be taxing and often inaccurate. During malaria, changes in fluid volume are rather multifarious and estimating this parameter, especially in si...Clinical assessment of fluid volume status in children during malaria can be taxing and often inaccurate. During malaria, changes in fluid volume are rather multifarious and estimating this parameter, especially in sick children is very challenging for clinicians who frequently rely on indices such as long capillary refill times, tachycardia, central venous pressure and decreased urine volume as guides. Here, we present the UHAS-MIDA, an open-source software tool that calculates the red blood cell (RBC) concentration and blood volume during malaria in children determined using a stable isotope of chromium (<sup>53</sup>Cr as the label) by gas chromatography-mass spectrometry in selective ion monitoring (GC/MS-SIM) analysis. A key component involves the determination of the compositions of the most abundant naturally occurring isotopes of Cr (<sup>50</sup>Cr, <sup>52</sup>Cr, <sup>53</sup>Cr), and converting the proportions into a 3 × 3 matrix. To estimate unknown proportions of chromium isotopic mixtures from the measured abundances of three ions, an inverse matrix was calculated. The inverse together with several inputs is then used to calculate the corrected MS ion abundances. Thus, we constructed the software tool UHAS- MIDA using HTML, CSS/Bootstrap, JavaScript, and PHP scripting languages. The tool enables the user to efficiently determine RBC concentration and fluid volume. The source code, binary packages and associated materials for UHAS-MIDA are freely available at https://github.com/bentil078/Abaye-et-al_UHASmida展开更多
基金support from the National Science Foundation of China(22078190)the National Key R&D Plan of China(2020YFB1505802).
文摘Joint time–frequency analysis is an emerging method for interpreting the underlying physics in fuel cells,batteries,and supercapacitors.To increase the reliability of time–frequency analysis,a theoretical correlation between frequency-domain stationary analysis and time-domain transient analysis is urgently required.The present work formularizes a thorough model reduction of fractional impedance spectra for electrochemical energy devices involving not only the model reduction from fractional-order models to integer-order models and from high-to low-order RC circuits but also insight into the evolution of the characteristic time constants during the whole reduction process.The following work has been carried out:(i)the model-reduction theory is addressed for typical Warburg elements and RC circuits based on the continued fraction expansion theory and the response error minimization technique,respectively;(ii)the order effect on the model reduction of typical Warburg elements is quantitatively evaluated by time–frequency analysis;(iii)the results of time–frequency analysis are confirmed to be useful to determine the reduction order in terms of the kinetic information needed to be captured;and(iv)the results of time–frequency analysis are validated for the model reduction of fractional impedance spectra for lithium-ion batteries,supercapacitors,and solid oxide fuel cells.In turn,the numerical validation has demonstrated the powerful function of the joint time–frequency analysis.The thorough model reduction of fractional impedance spectra addressed in the present work not only clarifies the relationship between time-domain transient analysis and frequency-domain stationary analysis but also enhances the reliability of the joint time–frequency analysis for electrochemical energy devices.
文摘BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.
基金supported by the National High Level Hospital Clinical Research Funding(No.BJ-2219-195 and No.BJ-2023-090).
文摘Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.
基金In 2021,Wuxi Medical Innovation Team CXTD2021023,Jiangsu Province maternal and Child Health research key funding project F201915.
文摘Objective:This study used comprehensive bioinformatics analysis and network pharmacology analysis to investigate the potentially relevant mechanisms of Sophora flavescens against cervical squamous cell carcinoma.Methods:Consistently altered genes involved in cervical squamous cell cancerization were analyzed in the GEO database.The chemical ingredients and target genes of Sophora flavescens were explored using the TCMSP database.We obtained the potential therapeutic targets of Sophora flavescens by intersecting the above genesets and validated them in the GEPIA database.The interaction between Sophora flavescens and target genes was predicted by molecular docking.RT-qPCR was used to verify the changes of target genes in HeLa cells treated with Sophora flavescens.Single-gene GSEA functional analysis were performed to determine the molecular mechanisms.Results:Fifteen genes related to the transformation of cervical squamous cell carcinoma were identified,among which AR and ESR1 were confirmed as targets for kaempferol,wighteone,formononetin,and phaseolinon.These compounds are the active ingredients in Sophora flavescens.Low expressions of AR and ESR1 correlate with a poor prognosis,while Sophora flavescens treatment increases the expression of AR and ESR1 in HeLa.GSEA analysis showed that AR and ESR1 mainly participate in the epithelial-mesenchymal transition in cervical squamous cell carcinoma.Conclusion:Sophora flavescens exert anti-tumor effects by targeting AR and ESR1,which may regulate cancer metastasis.
基金This study was supported by grants from the Key Project of the Chinese Ministry of Science and Technology(2017ZX102022022)National Key Research and Development Program of China(2021YFC2301801).
文摘Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.
文摘In the last two decades the study of red blood cell elasticity using optical tweezers has known a rise appearing in the scientific research with regard to the various works carried out. Despite the various work done, no study has been done so far to study the influence of friction on the red blood cell indentation response using optical tweezers. In this study, we have developed a new approach to determine the coefficient of friction as well as the frictional forces of the red blood cell. This approach therefore allowed us to simultaneously carry out the indentation and traction test, which allowed us to extract the interfacial properties of the microbead red blood cell couple, among other things, the friction coefficient. This property would be extremely important to investigate the survival and mechanical features of cells, which will be of great physiological and pathological significance. But taking into account the hypothesis of friction as defined by the isotropic Coulomb law. The experiment performed for this purpose is the Brinell Hardness Test (DB).
基金supported by the grants from Innovation Fund for Medical Sciences (CIFMS) from Chinese Academy of Medical Sciences (No.2021-I2M-1-062)National Key R&D Program of China from Ministry of Science and Technology of the People’s Republic of China (No.2022YFC2304601,2021YFC2500801)+1 种基金National High Level Hospital Clinical Research Funding (2022-PUMCH-D-005,2022-PUMCH-D-111,2022-PUMCH-B-126)National key clinical specialty construction projects from National Health Commission。
文摘BACKGROUND:Emergency patients with sepsis or septic shock are at high risk of death.Despite increasing attention to microhemodynamics,the clinical use of advanced microcirculatory assessment is limited due to its shortcomings.Since blood gas analysis is a widely used technique reflecting global oxygen supply and consumption,it may serve as a surrogate for microcirculation monitoring in septic treatment.METHODS:We performed a search using PubMed,Web of Science,and Google scholar.The studies and reviews that were most relevant to septic microcirculatory dysfunctions and blood gas parameters were identified and included.RESULTS:Based on the pathophysiology of oxygen metabolism,the included articles provided a general overview of employing blood gas analysis and its derived set of indicators for microhemodynamic monitoring in septic care.Notwithstanding flaws,several parameters are linked to changes in the microcirculation.A comprehensive interpretation of blood gas parameters can be used in order to achieve hemodynamic optimization in septic patients.CONCLUSION:Blood gas analysis in combination with clinical performance is a reliable alternative for microcirculatory assessments.A deep understanding of oxygen metabolism in septic settings may help emergency physicians to better use blood gas analysis in the evaluation and treatment of sepsis and septic shock.
基金The study was approved by the ethics committee of the First Affiliated Hospital of Chongqing Medical University(2022-K205),this study was conducted in accordance with the World Medical Association Declaration of Helsinki as well。
文摘BACKGROUND Previous studies have reported that low hematocrit levels indicate poor survival in patients with ovarian cancer and cervical cancer,the prognostic value of hematocrit for colorectal cancer(CRC)patients has not been determined.The prognostic value of red blood cell distribution width(RDW)for CRC patients was controversial.AIM To investigate the impact of RDW and hematocrit on the short-term outcomes and long-term prognosis of CRC patients who underwent radical surgery.METHODS Patients who were diagnosed with CRC and underwent radical CRC resection between January 2011 and January 2020 at a single clinical center were included.The short-term outcomes,overall survival(OS)and disease-free survival(DFS)were compared among the different groups.Cox analysis was also conducted to identify independent risk factors for OS and DFS.RESULTS There were 4258 CRC patients who underwent radical surgery included in our study.A total of 1573 patients were in the lower RDW group and 2685 patients were in the higher RDW group.There were 2166 and 2092 patients in the higher hematocrit group and lower hematocrit group,respectively.Patients in the higher RDW group had more intraoperative blood loss(P<0.01)and more overall complications(P<0.01)than did those in the lower RDW group.Similarly,patients in the lower hematocrit group had more intraoperative blood loss(P=0.012),longer hospital stay(P=0.016)and overall complications(P<0.01)than did those in the higher hematocrit group.The higher RDW group had a worse OS and DFS than did the lower RDW group for tumor node metastasis(TNM)stage I(OS,P<0.05;DFS,P=0.001)and stage II(OS,P=0.004;DFS,P=0.01)than the lower RDW group;the lower hematocrit group had worse OS and DFS for TNM stage II(OS,P<0.05;DFS,P=0.001)and stage III(OS,P=0.001;DFS,P=0.001)than did the higher hematocrit group.Preoperative hematocrit was an independent risk factor for OS[P=0.017,hazard ratio(HR)=1.256,95%confidence interval(CI):1.041-1.515]and DFS(P=0.035,HR=1.194,95%CI:1.013-1.408).CONCLUSION A higher preoperative RDW and lower hematocrit were associated with more postoperative complications.However,only hematocrit was an independent risk factor for OS and DFS in CRC patients who underwent radical surgery,while RDW was not.
基金Supported by National Natural Science Foundation of China,No.81702923,and No.81971503Open Project of State Key Laboratory of Medical Immunology,No.NKLMI2023K03+1 种基金Shanghai Shen Kang Hospital Development Center Clinical Science and Technology Innovation Project,No.SHDC12020104Basic Medical Research Project of Naval Medical University,No.2022QN072.
文摘The tumor microenvironment is a complex network of cells,extracellular matrix,and signaling molecules that plays a critical role in tumor progression and metastasis.Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits.However,recent studies have shown that lymphatic endothelial cells(LECs)and blood endothelial cells(BECs)also play multifaceted roles in the tumor microenvironment beyond their structural functions,particularly in hepatocellular carcinoma(HCC).This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC,including their involvement in angiogenesis,immune modulation,lymphangiogenesis,and metastasis.By providing a detailed account of the complex interplay between LECs,BECs,and tumor cells,this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.
基金Supported by Zhejiang Province Traditional Chinese Medicine Science and 158 Technology Project,No.2023ZL008.
文摘BACKGROUND Accumulating clinical evidence has shown that diabetes mellitus(DM)is a serious risk factor for cardiovascular disorders and an important factor for adverse cardiovascular events.AIM To explore the value of the combined determination of the neutrophil-lymphocyte ratio(NLR)and red blood cell distribution width(RDW)in the early diagnosis and prognosis evaluation of DM complicated with heart failure(HF).METHODS We retrospectively analyzed clinical data on 65 patients with type 2 DM(T2DM)complicated with HF(research group,Res)and 60 concurrent patients with uncomplicated T2DM(control group,Con)diagnosed at Zhejiang Provincial People’s Hospital between January 2019 and December 2021.The NLR and RDW values were determined and comparatively analyzed,and their levels in T2DM+HF patients with different cardiac function grades were recorded.The receiver operating characteristic(ROC)curves were plotted to determine the NLR and RDW values(alone and in combination)for the early diagnosis of HF.The correlation between NLR and RDW with the presence or absence of cardiac events was also investigated.RESULTS Higher NLR and RDW levels were identified in the Res vs the Con groups(P<0.05).The NLR and RDW increased gradually and synchronously with the deterioration of cardiac function in the Res group,with marked differences in their levels among patients with grade II,III,and IV HF(P<0.05).ROC curve analysis revealed that NLR combined with RDW detection had an area under the curve of 0.915,a sensitivity of 76.9%,and a specificity of 100%for the early diagnosis of HF.Furthermore,HF patients with cardiac events showed higher NLR and RDW values compared with HF patients without cardiac events.CONCLUSION NLR and RDW were useful laboratory indicators for the early diagnosis of DM complicated with HF,and their joint detection was beneficial for improving diagnostic efficiency.Additionally,NLR and RDW values were directly proportional to patient outcomes.
基金This work was supported by Zhejiang Energy Group(znkj-2018-118)Key Research and Development Program of Zhejiang Province(2021C01006)+5 种基金Key Project of Zhejiang Province(2021C04009)Science and technology projects in Liaoning Province 2021(2021JH1/10400104)Ningbo“Innovation 2025”Major Project(2020Z098)National Key R&D Program of China(2018YFB1500403)National Natural Science Foundation of China(61974178,61874177,62004199)Youth Innovation Promotion Association(2018333).
文摘In this work,we developed a simple and direct circuit model with a dual two-diode model that can be solved by a SPICE numerical simulation to comprehensively describe the monolithic perovskite/crystalline silicon(PVS/c-Si)tandem solar cells.We are able to reveal the effects of different efficiency-loss mechanisms based on the illuminated current density-voltage(J-V),semi-log dark J-V,and local ideality factor(m-V)curves.The effects of the individual efficiency-loss mechanism on the tandem cell’s efficiency are discussed,including the exp(V/VT)and exp(V/2VT)recombination,the whole cell’s and subcell’s shunts,and the Ohmic-contact or Schottky-contact of the intermediate junction.We can also fit a practical J-V curve and find a specific group of parameters by the trial-and-error method.Although the fitted parameters are not a unique solution,they are valuable clues for identifying the efficiency loss with the aid of the cell’s structure and experimental processes.This method can also serve as an open platform for analyzing other tandem solar cells by substituting the corresponding circuit models.In summary,we developed a simple and effective methodology to diagnose the efficiency-loss source of a monolithic PVS/c-Si tandem cell,which is helpful to researchers who wish to adopt the proper approaches to improve their solar cells.
文摘Alloantibodies that are non ABO Alloimmunization to protein antigens happens only after exposure, in contrast to ABO isohaemagglutinins, which are present naturally, even in the absence of prior exposure. It is recognized that while non-ABO RBC antibodies are less common than ABO antibodies, they generate essentially the same issues that lead to unfavorable clinical results. If non-ABO alloantibodies are identified early on, these issues related complications may be avoided This call for an in-depth understanding of the recipient and donor’s ABO-Rh grouping, antibody screening, and the phenotype of certain antigens. Equally important, the temporal association time between transplantation and hemolysis can help identify the underlying mechanism of hemolysis and direct appropriate management. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Finding the cause of post-HSCT anemia is essential for prevention and therapy, in addition to a thorough grasp of the mechanism of anemia in non-ABO-incompatible HSCT and the temporal link between HSCT and anemia. Therefore, for that, it is crucial to identify the etiology of post-HSCT anemia. In this case report review, we would like to highlight the vital role of transfusion medicine services and stem cell clinical teams in paying particular attention to the clinical significance of non-ABO alloantibodies involved to avoid causing overt hemolysis of incompatible donor RBCs or delayed erythropoiesis. Considering the fact that some of the Haematopoietic stem cell transplant centers do not give an attention to the other non-ABO RBC antigens.
基金Guizhou Provincial Department of Science and Technology Natural Science Foundation(No Foundation-ZK[2022])the Guizhou Provincial Health Commission Science and Technology Fund(No.GZWKJ2023-135)the Science Foundation of 925th Hospital(No.2023[3],No.2022[3/4]).
文摘Background:The cyclin-dependent kinase inhibitor 2a(CDKN2A)gene,identified as the multiple tumor suppressor gene,functions as a regulatory gene implicated in cancer pathogenesis.Its significance lies in its pivotal involvement in the genesis of various tumors;notwithstanding,the precise connection between CDKN2A and c olon adenocarcinoma(COAD)remains undisclosed.Methods:The objective of this research was to assess the predictive importance of CDKN2A in COAD by analyzing data from The Cancer Genome Atlas database.Logistic regression,signed rank test,Wilcoxon test,and Kruskal-Wallis test were used to examine CDKN2A expression levels and clinicopathological features.Univariate and multivariate Cox r egression analyses and Kaplan-Meier analysis found prognostic variables.Additionally,gene set enrichment analysis identified key CDKN2A expression pathways.The study additionally examined CDKN2A expression with tumor immune infiltration using The Cancer Genome Atlas data and single sample gene set enrichment analysis.Results:The results of this investigation indicated a substantial connection between higher CDKN2A expression and negative outcomes in terms of overall survival and disease-related survival among COAD patients.Gene set enrichment analysis indicated a tight link between CDKN2A and both the cell cycle and hedgehog signaling pathways.Subsequent evaluation employing single sample gene set enrichment analysis demonstrated a positive link between CDKN2A expression with infiltration by iDCs,whereas a negative correlation was detected with infiltration by helper T cells.Conclusion:In conclusion,the present study gives strong data supporting the predictive value of CDKN2A and its possible usefulness as a biomarker for COAD.Additionally,our results show a reasonable link between CDKN2A expression and immune influx in COAD,putting light on the role of CDKN2A in the control of the tumor microenvironment.Nevertheless,additional studies are needed to confirm the underlying mechanisms of these relationships and to discover the therapeutic possibilities of targeting CDKN2A in the treatment of COAD.
文摘Increasing evidence has shown that cell populations are not homogeneous,but rather heterogeneous,even within very small cell populations.Bulk measurements based on the homogenized cell population do not account for the critical changes occurring in individual cells and are sometimes misleading.Cellular heterogeneity characteristics may be the key to address previously unsolved questions in disease development and progression.
基金Thanks to Major Scientific and Technological Innovation Projects in Shandong Province(2018-CXGC0803)for the financial support of this article.
文摘Proton exchange membrane fuel cells(PEMFCs)are largely used in various applications because of their pollution-free products and high energy conversion efficiency.In order to improve the related design,in the present work a new spiral flow field with a bypass is proposed.The reaction gas enters the flow field in the central path and diffuses in two directions through the flow channel and the bypass.The bypasses are arranged incrementally.The number of bypasses and the cross-section size of the bypasses are varied parametrically while a single-cell model of the PEMFC is used.The influence of the concentration of liquid water and oxygen in the cell on the performance of different flow fields is determined by means of Computational fluid dynamics(COMSOL Multiphysics software).Results show that when the bypass number is 48 and its cross-sectional area is 0.5 mm^(2),the cell exhibits the best performances.
基金This project was supported by a program of Science Project of Hubei Province (No.2003AA301C10).
文摘The changes of CD4^+CD25^+ regulatory T cells (CD4^+CD25^+ Treg) and Foxp3 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with asthma were investigated in order to elucidate the possible roles of CD4^+CD25^+ Treg in the development of asthma. The peripheral blood samples were collected from 29 healthy controls (normal control group) and 78 patients with asthma which included 30 patients in exacerbation group, 25 patients in persistent group, and 23 patients in remission group. By using flow cytometry and RT-PCR, the CD4^+CD25^+ Treg ratio and Foxp3 mRNA in PBMCs were detected. The CD4^+CD25^+ Treg ratio and Foxp3 mRNA in PBMCs of exacerbation and persistent groups were lower than that of remission and normal control groups (P〈0.05). Although the CD4^+CD25^+ Treg ratio and Foxp3 mRNA of remission group were also lower than that of normal control group, there was no significant difference between them (P〉0.05). As compared with persistent group, exacerbation group had lower CD4^+CD25^+ Treg ratio and Foxp3 mRNA (P〈0.05). It was indicated that the decrease of CD4^+CD25^+ Treg ratio and its function in PBMCs may be responsible for pathogenesis of asthma.
基金supported by the National Natural Science Foundation of China,No.81471308a grant from the Science and Technology Plan Project of Dalian City in China,No.2015F11GH094
文摘There is a small amount of clinical data regarding the safety and feasibility of autologous peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis.The objectives of this retrospective study were to assess the safety and efficacy of peripheral blood mononuclear cell transplantation in 14 amyotrophic lateral sclerosis patients to provide more objective data for future clinical trials.After stem cell mobilization and collection,autologous peripheral blood mononuclear cells(1 × 109) were isolated and directly transplanted into the subarachnoid space of amyotrophic lateral sclerosis patients.The primary outcome measure was incidence of adverse events.Secondary outcome measures were electromyography 1 week before operation and 4 weeks after operation,Functional Independence Measurement,Berg Balance Scale,and Dysarthria Assessment Scale 1 week preoperatively and 1,2,4 and 12 weeks postoperatively.There was no immediate or delayed transplant-related cytotoxicity.The number of leukocytes,serum alanine aminotransferase and creatinine levels,and body temperature were within the normal ranges.Radiographic evaluation showed no serious transplant-related adverse events.Muscle strength grade,results of Functional Independence Measurement,Berg Balance Scale,and Dysarthria Assessment Scale were not significantly different before and after treatment.These findings suggest that peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis is safe,but its therapeutic effect is not remarkable.Thus,a large-sample investigation is needed to assess its efficacy further.
基金This project was supported by the National Natural Science Foundation of China the Natural Science Foundation of Shandong Province and the Key State Laboratory of Electroanalytical ChemistryChangchun Institute of Applied Chemistry,Chinese Academy
文摘A novel method for determination of amino acids in individual human red blood cells has been developed. In this method, the derivatization reagents (NDA and CN-) are introduced into living cells by electroporation. After completion of derivatization, the amino acids in a single cell is determined by capillary zone electrophoresis with end-column amperometric detection.
文摘Hepatitis C virus(HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment of dendritic cells(DCs) that play a central role in activating T cell responses. Although the impact of HCV on DC phenotype and function is likely to be more prominent in the liver, major HCV-induced alterations are detectable in peripheral blood DCs(pb DCs) that represent the most accessible source of DCs. These alterations include numerical reduction, impaired production of inflammatory cytokines and increased production of immunosuppressive IL10. These changes in DCs are relevant to our understanding the immune mechanisms underlying the propensity of HCV to establish persistent infection. Importantly, the noninvasive accessibility of pb DCs renders the analysis of these cells a convenient procedure that can be serially repeated in patient follow-up. Accordingly, the study of pb DCs in HCV-infected patients during conventional treatment with pegylated interferon and ribavirin indicated that restoration of normal plasmacytoid DC count may represent an additional mechanism contributing to the efficacy of the dual therapy. It also identified the pre-treatment levels of plasmacytoid DCs and IL10 as putative predictors of response to therapy. Treatment of chronic HCV infection is changing, as new generation direct-acting antiviral agents will soon be available for use in interferon-free therapeutic strategies. The phenotypic and functional analysis of pb DCs in this novel therapeutic setting will provide a valuable tool for investigating mechanisms underlying treatment efficacy and for identifying predictors of treatment response.
文摘Clinical assessment of fluid volume status in children during malaria can be taxing and often inaccurate. During malaria, changes in fluid volume are rather multifarious and estimating this parameter, especially in sick children is very challenging for clinicians who frequently rely on indices such as long capillary refill times, tachycardia, central venous pressure and decreased urine volume as guides. Here, we present the UHAS-MIDA, an open-source software tool that calculates the red blood cell (RBC) concentration and blood volume during malaria in children determined using a stable isotope of chromium (<sup>53</sup>Cr as the label) by gas chromatography-mass spectrometry in selective ion monitoring (GC/MS-SIM) analysis. A key component involves the determination of the compositions of the most abundant naturally occurring isotopes of Cr (<sup>50</sup>Cr, <sup>52</sup>Cr, <sup>53</sup>Cr), and converting the proportions into a 3 × 3 matrix. To estimate unknown proportions of chromium isotopic mixtures from the measured abundances of three ions, an inverse matrix was calculated. The inverse together with several inputs is then used to calculate the corrected MS ion abundances. Thus, we constructed the software tool UHAS- MIDA using HTML, CSS/Bootstrap, JavaScript, and PHP scripting languages. The tool enables the user to efficiently determine RBC concentration and fluid volume. The source code, binary packages and associated materials for UHAS-MIDA are freely available at https://github.com/bentil078/Abaye-et-al_UHASmida