Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in ...Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in tumor diagnosis and treatment.Given the critical role of molecular subtyping in the BCa treatment,acquiring a comprehensive understanding is imperative for guiding treatment decisions,optimizing risk assessment systems,and ultimately improving patient prognosis.Methods:In this review,we provide a comprehensive overview of the research progress in molecular subtyping of BCa,with a primary focus on discussing its utility in guiding various treatment modalities including neoadjuvant chemotherapy,neoadjuvant immunotherapy,and targeted therapy.In addition,this review also covers the trimodality treatment,antibody-drug conjugates,and the treatment of small cell BCa.Results:We present a comprehensive overview of the responsiveness or resistance of different molecular subtypes of BCa to various therapeutic modalities.The basal subtype demonstrates favorable sensitivity to neoadjuvant chemotherapy across multiple classification systems,whereas the luminal infiltrated subtype exhibits potential susceptibility to immunotherapy.In terms of targeted therapy,the basal-like and the basal/squamous subtypes in some classifications have shown notable responsiveness to epidermal growth factor receptor-targeted therapy.Moreover,the luminal subtype in the University of Texas M.D.Anderson Cancer Center classification,the luminal papillary subtypes according to the Cancer Genome Atlas Research Network classification in 2017,and the luminal unstable type in the 2019 Molecular Subtyping classification show potential for the fibroblast growth factor receptor 3-targeted treatment.Conclusion:The significance and impact of BCa molecular subtyping in guiding treatment,evaluating progression,and predicting prognosis are increasingly acknowledged.Accurate subtyping and broad application can bring good benefits to clinical decision-making,risk assessment,and prognostic evaluation.展开更多
This study developed a multiplex RT-PCR integrated with luminex technology to rapidly subtype simultaneously multiple influenza viruses. Primers and probes were designed to amplify NS and M genes of influenza A viruse...This study developed a multiplex RT-PCR integrated with luminex technology to rapidly subtype simultaneously multiple influenza viruses. Primers and probes were designed to amplify NS and M genes of influenza A viruses HA gene of ill, H3, H5, HT, H9 subtypes, and NA gene of the N1 and N2 subtypes. Universal super primers were introduced to establish a multiplex RT-PCR （GM RT-PCR）. It included three stages of RT-PCR amplification, and then the RT-PCR products were further tested by LiquiChip probe, combined to give an influenza virus （IV） rapid high throughput subtyping test, designated as GMPLex. The IV GMPLex rapid high throughput subtyping test presents the following features： high throughput, able to determine the subtypes of 9 target genes in H1, H3, H5, H7, H9, N1, and N2 subtypes of the influenza A virus at one time; rapid, completing the influenza subtyping within 6 hours; high specificity, ensured the specificity of the different subtypes by using two nested degenerate primers and one probe, no cross reaction occurring between the subtypes, no non-specific reactions with other pathogens and high sensitivity. When used separately to detect the product of single GM RT-PCR for single H5 or N1 gene, the GMPLex test showed a sensitivity of 10-5（= 280ELDs0） forboth tests and the Luminex qualitative ratio results were 3.08 and 3.12, respectively. When used to detect the product of GM RT-PCR for H5N1 strain at the same time, both showed a sensitivity of 10-4（=2800 ELD50）. The GMPLex rapid high throughput subtyping test can satisfy the needs of influenza rapid testing.展开更多
Autism spectrum disorder can be differentiated into three subtypes （aloof, passive, and active-but-odd） based on social behaviors according to the Wing Subgroups Questionnaire （WSQ）. However, the correlations betw...Autism spectrum disorder can be differentiated into three subtypes （aloof, passive, and active-but-odd） based on social behaviors according to the Wing Subgroups Questionnaire （WSQ）. However, the correlations between the scores on some individual items and the total score are poor. In the present study, we translated the WSQ into Chinese, modified it, validated it in autistic and typically- developing Chinese children, and renamed it the Beijing Autism Subtyping Questionnaire （BASQ）. Our results demonstrated that the BASQ had improved validity and reliability, and differentiated autistic children into these three subtypes more precisely. We noted that the autistic symptoms tended to be severe in the aloof, moderate in the passive, and mild in the active-but-odd subtypes. The modified questionnaire may facilitate etiological studies and the selection of therapeutic regimes.展开更多
Listeria monocytogenes,one of the most important foodborne pathogens,can cause listeriosis,a lethal disease for humans.L.ivanovii,which is closely related to L.monocytogenes,is also widely distributed in nature and in...Listeria monocytogenes,one of the most important foodborne pathogens,can cause listeriosis,a lethal disease for humans.L.ivanovii,which is closely related to L.monocytogenes,is also widely distributed in nature and infects mainly warm-blooded ruminants,causing economic loss.Thus,there are high priority needs for methodologies for rapid,specific,cost-effective and accurate detection,characterization and subtyping of L.monocytogenes and L.ivanovii in foods and environmental sources.In this review,we(A)described L.monocytogenes and L.ivanovii,world-wide incidence of listeriosis,and prevalence of various L.monocytogenes strains in food and environmental sources;(B)comprehensively reviewed different types of traditional and newly developed methodologies,including culture-based,antigen/antibody-based,LOOP-mediated isothermal amplification,matrix-assisted laser desorption ionization-time of flight-mass spectrometry,DNA microarray,and genomic sequencing for detection and characterization of L.monocytogenes in foods and environmental sources;(C)comprehensively summarized different subtyping methodologies,including pulsed-field gel electrophoresis,multi-locus sequence typing,ribotyping,and phage-typing,and whole genomic sequencing etc.for subtyping of L.monocytogenes strains from food and environmental sources;and(D)described the applications of these methodologies in detection and subtyping of L.monocytogenes in foods and food processing facilities.展开更多
Objective To optimize the performance of Pulsed-Field Gel Electrophoresis （PFGE） for the comparison of inter-laboratory results and information exchange of Borrelia burgdorferi subtypingo Methods A panel of 34 strai...Objective To optimize the performance of Pulsed-Field Gel Electrophoresis （PFGE） for the comparison of inter-laboratory results and information exchange of Borrelia burgdorferi subtypingo Methods A panel of 34 strains of B. burgdorferi were used to optimize PFGE for subtyping. In order to optimize the electrophoretic parameters （EPs）, all 34 strains of B. burgdorferi were analyzed using four EPs, yielding different Simpson diversity index （D） values and the epidemiological concordance was also evaluated. Results The EP of a switch time of l s to 25 s for13 h and l s to10 s for 6 h produced the highest D value and was declared to be optimal for Mlul and 5mal PFGE of B. burgdorferi. Mlul and Smal were selected as the first and second restriction enzymes for PFGE subtyping of B. burgdorferi according to discrimination and consistency with epidemiological data. Conclusion PFGE can be used as a valuable test for routine genospecies identification of B burgdorferi.展开更多
Objective To establish and compare the pulsed-field gel electrophoresis （PFGE）, multiple-locus variable number tandem repeat analysis （MLVA） and automated ribotyping for subtyping of Citrobacter strains. Methods P...Objective To establish and compare the pulsed-field gel electrophoresis （PFGE）, multiple-locus variable number tandem repeat analysis （MLVA） and automated ribotyping for subtyping of Citrobacter strains. Methods PFGE protocol was optimized in terms of plug preparation procedure, restriction enzymes and configuration of electrophoretic parameters. MLVA method was evaluated by finding variable number tandem repeats in two genomes of Citrobacter strains. The ribotyping was performed by using the automated RiboPrinter system. Results We optimized the plug preparation procedure, focused on the cell suspension concentration （turbidity of 2.5 to 3.5）, SDS addition （no SDS needed） and lysis time （1 h）, and selected the appropriate restriction enzyme （Xbal） and the electrophoretic parameters （1.0 s-20.0 s for 19 h） of PFGE. There was nearly no discriminatory power of MLVA between Citrobacter strains. For 51 Citrobacter strains, automated ribotyping gave a D-value of 0.9945, while PFGE gave a D-value of 0.9969. Both PFGE and automated ribotyping clustered strains from the same sources （with the same species from the same place at the same time identified as the same source） and divided strains from different sources （from different years, places and hosts） into different subtypes. Conclusion PFGE protocol established in this paper and automated ribotyping are suitable for application in Citrobacter subtyping.展开更多
Objective: To investigate U parvum (previously Ureaplasmaurealyticum biovar 1) and U urealyticum (previouslyUreaplasma urealyticum biovar 2) and their subtypes andserovars in urine specimens of pregnant women. Methods...Objective: To investigate U parvum (previously Ureaplasmaurealyticum biovar 1) and U urealyticum (previouslyUreaplasma urealyticum biovar 2) and their subtypes andserovars in urine specimens of pregnant women. Methods: After collecting 151 specimens and inoculatingbroth, all broth culture positive (urease positive) specimenswere amplified, species were identified and subtyped by usinggeneral primers, species-specific, and type-specific primerstargeting the multiple banded antigen (MBA) gene sequence. Results: U parvum was identified in 58 of 151 specimens andU. urealyticum in 18 (both were present in 5, and neither werefound in 6). Serovars 3, 1, and 6 were the most commonamong U parvum isolates and subtypes l and 3 were the mostcommon among U urealyticum. Multiple serovars amongclinical isolates were found. Conclusion: This PCR-based typing system could facilitatestudies of the relationship between individual ureaplasmaspecies or subtypes and human diseases.展开更多
Molecular subtyping of cancer can greatly help to understand the development of disease and predict tumor behavior.Exploring detection methods for precise subtyping is appealing to prognosis and personalized therapy.D...Molecular subtyping of cancer can greatly help to understand the development of disease and predict tumor behavior.Exploring detection methods for precise subtyping is appealing to prognosis and personalized therapy.During the past decades,DNA-based biosensors have exhibited great potential in cancer diagnosis due to their structural programmability and functional diversity.Despite the encouraging progress that has been made,there remains an issue in improving the accuracy and sensitivity of cancer subtyping due to the complex process of disease,especially in preclinical or clinical applications.To accelerate the development of DNA sensors in the identification of cancer subtypes,in this review,we summarized their advances in molecular subtyping by analyzing the heterogeneity in categories and levels of biomarkers between cancer subtypes.The strategies toward genomic and proteomic heterogeneity in cells or on the cell surface,as well as the cancer excretions including extracellular vesicles(EVs)and microRNA(miRNAs)in serum,are summarized.Current challenges and the opportunities of DNA-based sensors in this field are also discussed.展开更多
Objective To analyze the value of multi-slice spiral CT ( SCT) scan in staging and subtyping of renal cell carcinoma ( RCC) . Methods The preoperative kidney SCT data and postoperative pathology results of 64 patients...Objective To analyze the value of multi-slice spiral CT ( SCT) scan in staging and subtyping of renal cell carcinoma ( RCC) . Methods The preoperative kidney SCT data and postoperative pathology results of 64 patients with RCC were retrospectively analyzed. The pa-展开更多
The prevalence of type 2 diabetes mellitus(T2DM)is increasing rapidly worldwide.Because of the limited success of generic interventions,the focus of the disease study has shifted toward personalized strategies,particu...The prevalence of type 2 diabetes mellitus(T2DM)is increasing rapidly worldwide.Because of the limited success of generic interventions,the focus of the disease study has shifted toward personalized strategies,particularly in the early stages of the disease.Traditional Chinese medicine(TCM)is based on a systems view combined with personalized strategies and has improved our knowledge of personalized diagnostics.From a systems biology perspective,the understanding of personalized diagnostics can be improved to yield a biochemical basis for such strategies;for example,metabolomics can be used in combination with other system-based diagnostic methods such as ultra-weak photon emission(UPE).In this study,we investigated the feasibility of using plasma metabolomics obtained from 44 pre-T2DM subjects to stratify the following TCM-based subtypes:Qi-Yin deficiency,Qi-Yin deficiency with dampness,and Qi-Yin deficiency with stagnation.We studied the relationship between plasma metabolomics and UPE with respect to TCM-based subtyping in order to obtain biochemical information for further interpreting disease subtypes.Principal component analysis of plasma metabolites revealed differences among the TCM-based pre-T2DM subtypes.Relatively high levels of lipids(e.g.,cholesterol esters and triglycerides)were important discriminators of two of the three subtypes and may be associated with a higher risk of cardiovascular disease.Plasma metabolomics data indicate that the lipid profile is an essential component captured by UPE with respect to stratifying subtypes of T2DM.The results suggest that metabolic differences exist among different TCM-based subtypes of pre-T2DM,and profiling plasma metabolites can be used to discriminate among these subtypes.Plasma metabolomics thus provides biochemical insights into system-based UPE measurements.展开更多
Objective:To investigate Blastocystis’etiologic role and association with gastrointestinal symptomatology in acute and chronic urticaria patients and to identify Blastocystis subtypes responsible for urticaria.Method...Objective:To investigate Blastocystis’etiologic role and association with gastrointestinal symptomatology in acute and chronic urticaria patients and to identify Blastocystis subtypes responsible for urticaria.Methods:The study included urticaria patients and healthy individuals that presented to our polyclinic between June 2015 and May 2017.The participants were assigned into Group栺(137 patients),subdivided into acute(72)and chronic urticaria patients(65),and Group栻(129 control individuals).Blastocystis presence was investigated by native-Lugol examination,trichrome staining,PCR using sequence tagged site primers,and DNA sequencing analysis.The phylogenetic tree was constructed.Results:The native-Lugol and trichrome staining methods revealed that 16 patients(16/133,12.0%)had Blastocystis-positive stool samples,of which seven samples(7/133,5.3%)belonged acute and nine(9/133,6.8%)to chronic urticaria patients.Concerning Blastocystis subtypes,of the acute urticaria patients,three had subtype 1(ST1),one had ST2,and three had ST3.Of the chronic urticaria patients,one had ST1 and eight had ST3.Blastocystis positivity was detected in two control individuals(2/123,1.6%),both being ST3.All subtypes identified by PCR were confirmed by the sequencing analysis.The acute and chronic urticaria groups showed no statistically significant differences for Blastocystis positivity(P=0.60)and subtype distribution(P=0.15).A statistically significant difference was found between the urticaria patients and the controls for Blastocystis positivity(P<0.01),but not for subtype distribution(P=0.67)or for Blastocystis presence and gastrointestinal complaints.Conclusions:This study on Blastocystis subtype distribution among Turkish urticaria patients showed results consistent with the literature.It was concluded that Blastocystis should be kept in mind in patients with urticaria.展开更多
Background: Breast cancer is a genetically and clinically heterogeneous disease with multiple subtypes. The classification of these subtypes has evolved over the years. The most common and widely accepted classificati...Background: Breast cancer is a genetically and clinically heterogeneous disease with multiple subtypes. The classification of these subtypes has evolved over the years. The most common and widely accepted classification of breast cancer is from an immunohistochemical perspective, based on the expression of the following hormone receptors: Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor (HER2). Accordingly, the following four subtypes of breast cancer are widely recognized—Luminal A, Luminal B, HER2 Enriched and Triple Negative. Breast cancer management approaches include surgery, chemotherapy, radiotherapy and targeted hormone therapy necessitated by molecular subtyping. Aims: This study aimed to determine the level of adherence to breast cancer molecular subtyping among women with breast cancer attending tertiary health facilities in Imo State. Methodology: Immunohistochemistry reports of women with breast cancer attending tertiary health facilities in Imo State were retrieved from patient’s case files. Tissue blocks were also retrieved from tissue block archives of both hospitals for women who did not take up immunohistochemistry services after their initial diagnosis and also those whose immunohistochemistry reports were not found in their case files. Results: Among the 121 women that participated in the study, there were in all 74 (61.2%) had molecular subtyping of their tumour blocks. Up to 45 (37.2%) did not go for molecular subtyping of their tumour blocks while 2 (1.7%) were not sure whether they had or not. Conclusion: It, therefore, depicts that the rate of uptake was found as 61.2% among the participants and there is a need to create more awareness of the importance of molecular subtyping, which necessitates the use of targeted hormone therapy.展开更多
Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may a...Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may affect APOD expression.Therefore,this paper aims to investigate the significance of APOD expression and APOD DNA methylation in breast cancer.Methods:This study utilized comprehensive bioinformatics analysis of APOD using Gene Expression database of Normal and Tumor tissues 2,UCSC Xena,etc.Clinical and survival information obtained from the The Cancer Genome Atlas and Gene Expression Omnibus datasets were extracted for data mining.Results:The correlation between APOD and breast cancer was examined,along with the connection between APOD DNA methylation and APOD expression.In the The Cancer Genome Atlas cohort,as well as GSE31448 and GSE65194 datasets,APOD expression decreased in breast cancer(P<0.0001).Clinical feature analysis results showed that APOD expression was correlated with the PAM50 subtype,with the lowest expression in the Basal subtype(P<0.0001).High APOD expression is a good prognostic marker for breast cancer(HR=0.71,P=0.037).APOD methylation level was significantly negatively correlated with expression level(R=−0.4770,P<0.001),and cg15231202,cg23720929,and cg05624196 were important regulatory targets.High APOD expression was associated with higher metabolism and extracellular matrix scores.Conclusion:APOD is an independent prognostic marker for breast cancer and is regulated by DNA methylation to modulate mRNA expression.展开更多
OBJECTIVE:To research the subtyping and treatment of depression by leveraging studying on extensive Traditional Chinese Medicine(TCM)experiences through artificial intelligence(AI).METHODS:We retrieved depression-rela...OBJECTIVE:To research the subtyping and treatment of depression by leveraging studying on extensive Traditional Chinese Medicine(TCM)experiences through artificial intelligence(AI).METHODS:We retrieved depression-related literature published from inception to April 2023 from databases.From these sources,we extracted symptoms,signs,and prescriptions associated with depression.By utilizing the tree number system in the medical subject headings(MeSH),we established a hierarchical relationship matrix for symptoms/signs,as well as depression sample fingerprints.Using an unsupervised clustering algorithm,we constructed a machine learning model for classifying depression patients.Furthermore,we conducted an analysis of medication rules for each depression cluster.RESULTS:We created a My Structured Query Language(MySQL)database containing datasets of depression-symptoms/signs and depression-herbs,through mining 3522 published clinical literatures on TCM diagnosis and treatment for depression.We established hierarchical relationships among symptoms/signs of depression patients.Our unsupervised clustering analysis revealed that depression patients could be classified into 9 subtypes,with each subtype corresponding to a specific treatment prescription.Notably,one of the depression subtypes was consistently treated by Qi-tonifying formulas and herbs.This finding was further supported by data from Qi-deficiency patients,as there was a high similarity in the top symptoms/signs shared between this subtype and Qi-deficiency diagnosed by TCM.CONCLUSIONS:This study identified the subtypes and TCM treatment of depression by using machine learning and text mining.展开更多
Dear Editor,Growing clinical evidence shows that brain disorders are heterogeneous in phenotype,genetics,and neuropathology[1].Diagnosis and treatment tend to be affected by symptom presentation and the heterogeneity ...Dear Editor,Growing clinical evidence shows that brain disorders are heterogeneous in phenotype,genetics,and neuropathology[1].Diagnosis and treatment tend to be affected by symptom presentation and the heterogeneity of pathology,potentially hindering clinical trials in the development of medical treatment.Brain-based subtyping studies utilize magnetic resonance imaging(MRI)and data-driven methods to discover the subtypes of diseases,providing a new perspective on disease heterogeneity.展开更多
During the process of carcinogenesis and tumor progression,various molecular alternations occur in different omics levels.In recent years,multiomics approaches including genomics,epigenetics,transcriptomics,proteomics...During the process of carcinogenesis and tumor progression,various molecular alternations occur in different omics levels.In recent years,multiomics approaches including genomics,epigenetics,transcriptomics,proteomics,metabolomics,single-cell omics,and spatial omics have been applied in mapping diverse omics profiles of cancers.The development of high-throughput technologies such as sequencing and mass spectrometry has revealed different omics levels of tumor cells or tissues separately.While focusing on a single omics level results in a lack of accuracy,joining multiple omics approaches together undoubtedly benefits accurate molecular subtyping and precision medicine for cancer patients.With the deepening of tumor research in recent years,taking pathological classification as the only criterion of diagnosis and predicting prognosis and treatment response is found to be not accurate enough.Therefore,identifying precise molecular subtypes by exploring the molecular alternations during tumor occurrence and development is of vital importance.The review provides an overview of the advanced technologies and recent progress in multiomics applied in cancer molecular subtyping and detailedly explains the application of multiomics in identifying cancer driver genes and metastasis-related genes,exploring tumor microenvironment,and selecting liquid biopsy biomarkers and potential therapeutic targets.展开更多
Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now refe...Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now referred to as Gulf War Illness(GWI).As the underlying mechanisms of GWI have yet to be fully elucidated,diagnosis and treatment are based on symptomatic presentation.One confounding factor tied to the illness is the high presence of post-traumatic stress disorder(PTSD).Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction.As such,this research endeavor aimed to provide insight into the complex relationship between GWI symptoms,cytokine presence,and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.Methods:Symptom measures were gathered through the Multidimensional fatigue inventory(MFI)and 36-item short form health survey(SF-36)scales and biological measures were obtained through cytokine&cytometry analysis.Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders(DSM)-5,into GWI with high probability of PTSD symptoms(GWIH)and GWI with low probability of PTSD symptoms(GWIL).Data was analyzed using analysis of variance(ANOVA)statistical analysis along with correlation graph analysis.We mapped correlations between immune cells and cytokine signaling measures,hormones and GWI symptom measures to identify patterns in regulation between the GWIH,GWIL,and healthy control groups.Results:GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both healthy control(HC)and the GWIL subgroup.Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity(ANOVA F=4.7,P=0.01)indicating its potential usage as a biomarker for general GWI from control.While the unique identification of GWI with PTSD symptoms was less clear,the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge(ANOVA F>3.75,P<0.03).Additional differences in natural killer(NK)cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.Conclusions:We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.展开更多
Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predi...Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predict BCa molecular subtypes.Method:We developed a predictive model for BCa molecular subtypes using machine learning(ML)and pathomics derived from Hematoxylin-Eosin stained pathological slides.A cohort of 353 patients from TCGA was employed,and image features were extracted for analysis.Pathomic signatures were constructed using the LASSO Cox regression algorithm,and a pathomic-clinical nomogram was developed and validated in training and testing cohorts.Results:Seventy distinct image features were identified from 150 pathomic signatures.The model demonstrated robust predictive ability,with AUCs of 0.833 and 0.822 in the training and validation cohorts,respectively.The addition of pathomic score,N stage,and M stage improved the model’s discrimination,achieving AUCs of 0.877 and 0.794 in the training and validation cohorts.Limitations include the lack of an external validation cohort.Conclusion:Our ML-based pathomics model shows promise in predicting BCa molecular subtypes and has the potential to enhance prognosis prediction and inform treatment strategies,marking a significant step towards precision medicine for BCa.展开更多
Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 ...Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 is insufficient to predict therapeutic outcomes3,4.A recently identified vulnerability in SCLC involves the dysregulation of nuclear-cytoplasmic transport,particularly through exportin 1(XPO1)5-7.展开更多
Hepatocellular carcinoma(HCC)is one of the most prevalent and fatal digestive tumors.Treatment for this disease has been constraint by heterogeneity of this group of tumors,which has greatly limited the progress in pe...Hepatocellular carcinoma(HCC)is one of the most prevalent and fatal digestive tumors.Treatment for this disease has been constraint by heterogeneity of this group of tumors,which has greatly limited the progress in personalized therapy.Although existing studies have revealed the genetic and epigenetic blueprints that drive HCCs,many of the molecular mechanisms that lead to HCCs remain elusive.Recent advances in techniques for studying functional genomics,such as genome sequencing and transcriptomic analyses,have led to the discovery of molecular mechanisms that participate in the initiation and evolution of HCC.Integrative multi-omics analyses have identified several molecular subtypes of HCC associated with specific molecular characteristics and clinical outcomes.Deciphering similar molecular features among highly heterogeneous HCC patients is a prerequisite to implementation of personalized therapeutics.This review summarizes the current research progresses in precision therapy on the backbone of molecular subtypes of HCC.展开更多
基金supported by the grants from the National Natural Science Foundation of China(82273132 to Liu B).
文摘Objective:Bladder cancer(BCa)is a prevalent malignant tumor in the urinary system.Molecular subtyping,utilizing molecular characteristics,represents a novel classification system that has demonstrated its efficacy in tumor diagnosis and treatment.Given the critical role of molecular subtyping in the BCa treatment,acquiring a comprehensive understanding is imperative for guiding treatment decisions,optimizing risk assessment systems,and ultimately improving patient prognosis.Methods:In this review,we provide a comprehensive overview of the research progress in molecular subtyping of BCa,with a primary focus on discussing its utility in guiding various treatment modalities including neoadjuvant chemotherapy,neoadjuvant immunotherapy,and targeted therapy.In addition,this review also covers the trimodality treatment,antibody-drug conjugates,and the treatment of small cell BCa.Results:We present a comprehensive overview of the responsiveness or resistance of different molecular subtypes of BCa to various therapeutic modalities.The basal subtype demonstrates favorable sensitivity to neoadjuvant chemotherapy across multiple classification systems,whereas the luminal infiltrated subtype exhibits potential susceptibility to immunotherapy.In terms of targeted therapy,the basal-like and the basal/squamous subtypes in some classifications have shown notable responsiveness to epidermal growth factor receptor-targeted therapy.Moreover,the luminal subtype in the University of Texas M.D.Anderson Cancer Center classification,the luminal papillary subtypes according to the Cancer Genome Atlas Research Network classification in 2017,and the luminal unstable type in the 2019 Molecular Subtyping classification show potential for the fibroblast growth factor receptor 3-targeted treatment.Conclusion:The significance and impact of BCa molecular subtyping in guiding treatment,evaluating progression,and predicting prognosis are increasingly acknowledged.Accurate subtyping and broad application can bring good benefits to clinical decision-making,risk assessment,and prognostic evaluation.
基金The Basic Rasearch Project of Shenzhen(JC200903190778A)
文摘This study developed a multiplex RT-PCR integrated with luminex technology to rapidly subtype simultaneously multiple influenza viruses. Primers and probes were designed to amplify NS and M genes of influenza A viruses HA gene of ill, H3, H5, HT, H9 subtypes, and NA gene of the N1 and N2 subtypes. Universal super primers were introduced to establish a multiplex RT-PCR （GM RT-PCR）. It included three stages of RT-PCR amplification, and then the RT-PCR products were further tested by LiquiChip probe, combined to give an influenza virus （IV） rapid high throughput subtyping test, designated as GMPLex. The IV GMPLex rapid high throughput subtyping test presents the following features： high throughput, able to determine the subtypes of 9 target genes in H1, H3, H5, H7, H9, N1, and N2 subtypes of the influenza A virus at one time; rapid, completing the influenza subtyping within 6 hours; high specificity, ensured the specificity of the different subtypes by using two nested degenerate primers and one probe, no cross reaction occurring between the subtypes, no non-specific reactions with other pathogens and high sensitivity. When used separately to detect the product of single GM RT-PCR for single H5 or N1 gene, the GMPLex test showed a sensitivity of 10-5（= 280ELDs0） forboth tests and the Luminex qualitative ratio results were 3.08 and 3.12, respectively. When used to detect the product of GM RT-PCR for H5N1 strain at the same time, both showed a sensitivity of 10-4（=2800 ELD50）. The GMPLex rapid high throughput subtyping test can satisfy the needs of influenza rapid testing.
基金supported by the grant from the University of Ulm–Peking University Health Science Center Joint Center for Neuroscience Fund(BMU20160563)the grant from the National Natural Science Foundation of China(81601196)
文摘Autism spectrum disorder can be differentiated into three subtypes （aloof, passive, and active-but-odd） based on social behaviors according to the Wing Subgroups Questionnaire （WSQ）. However, the correlations between the scores on some individual items and the total score are poor. In the present study, we translated the WSQ into Chinese, modified it, validated it in autistic and typically- developing Chinese children, and renamed it the Beijing Autism Subtyping Questionnaire （BASQ）. Our results demonstrated that the BASQ had improved validity and reliability, and differentiated autistic children into these three subtypes more precisely. We noted that the autistic symptoms tended to be severe in the aloof, moderate in the passive, and mild in the active-but-odd subtypes. The modified questionnaire may facilitate etiological studies and the selection of therapeutic regimes.
文摘Listeria monocytogenes,one of the most important foodborne pathogens,can cause listeriosis,a lethal disease for humans.L.ivanovii,which is closely related to L.monocytogenes,is also widely distributed in nature and infects mainly warm-blooded ruminants,causing economic loss.Thus,there are high priority needs for methodologies for rapid,specific,cost-effective and accurate detection,characterization and subtyping of L.monocytogenes and L.ivanovii in foods and environmental sources.In this review,we(A)described L.monocytogenes and L.ivanovii,world-wide incidence of listeriosis,and prevalence of various L.monocytogenes strains in food and environmental sources;(B)comprehensively reviewed different types of traditional and newly developed methodologies,including culture-based,antigen/antibody-based,LOOP-mediated isothermal amplification,matrix-assisted laser desorption ionization-time of flight-mass spectrometry,DNA microarray,and genomic sequencing for detection and characterization of L.monocytogenes in foods and environmental sources;(C)comprehensively summarized different subtyping methodologies,including pulsed-field gel electrophoresis,multi-locus sequence typing,ribotyping,and phage-typing,and whole genomic sequencing etc.for subtyping of L.monocytogenes strains from food and environmental sources;and(D)described the applications of these methodologies in detection and subtyping of L.monocytogenes in foods and food processing facilities.
基金supported by the National Natural Science Foundation of China (NSFC)(31100105)the 12th Five-Year Major National Science and Technology Projects of China(No.2012ZX10004219-007)
文摘Objective To optimize the performance of Pulsed-Field Gel Electrophoresis （PFGE） for the comparison of inter-laboratory results and information exchange of Borrelia burgdorferi subtypingo Methods A panel of 34 strains of B. burgdorferi were used to optimize PFGE for subtyping. In order to optimize the electrophoretic parameters （EPs）, all 34 strains of B. burgdorferi were analyzed using four EPs, yielding different Simpson diversity index （D） values and the epidemiological concordance was also evaluated. Results The EP of a switch time of l s to 25 s for13 h and l s to10 s for 6 h produced the highest D value and was declared to be optimal for Mlul and 5mal PFGE of B. burgdorferi. Mlul and Smal were selected as the first and second restriction enzymes for PFGE subtyping of B. burgdorferi according to discrimination and consistency with epidemiological data. Conclusion PFGE can be used as a valuable test for routine genospecies identification of B burgdorferi.
基金supported by the project (grant 2005CB522904 and 2005CB522905) from the Ministry of Scientific Technologythe project (grant 2008ZX10004-001, 2008ZX10004-008, and 2009ZX10004-101) from the Ministry of Scientific Technology and the Ministry of Health of the People’s Republic of China
文摘Objective To establish and compare the pulsed-field gel electrophoresis （PFGE）, multiple-locus variable number tandem repeat analysis （MLVA） and automated ribotyping for subtyping of Citrobacter strains. Methods PFGE protocol was optimized in terms of plug preparation procedure, restriction enzymes and configuration of electrophoretic parameters. MLVA method was evaluated by finding variable number tandem repeats in two genomes of Citrobacter strains. The ribotyping was performed by using the automated RiboPrinter system. Results We optimized the plug preparation procedure, focused on the cell suspension concentration （turbidity of 2.5 to 3.5）, SDS addition （no SDS needed） and lysis time （1 h）, and selected the appropriate restriction enzyme （Xbal） and the electrophoretic parameters （1.0 s-20.0 s for 19 h） of PFGE. There was nearly no discriminatory power of MLVA between Citrobacter strains. For 51 Citrobacter strains, automated ribotyping gave a D-value of 0.9945, while PFGE gave a D-value of 0.9969. Both PFGE and automated ribotyping clustered strains from the same sources （with the same species from the same place at the same time identified as the same source） and divided strains from different sources （from different years, places and hosts） into different subtypes. Conclusion PFGE protocol established in this paper and automated ribotyping are suitable for application in Citrobacter subtyping.
文摘Objective: To investigate U parvum (previously Ureaplasmaurealyticum biovar 1) and U urealyticum (previouslyUreaplasma urealyticum biovar 2) and their subtypes andserovars in urine specimens of pregnant women. Methods: After collecting 151 specimens and inoculatingbroth, all broth culture positive (urease positive) specimenswere amplified, species were identified and subtyped by usinggeneral primers, species-specific, and type-specific primerstargeting the multiple banded antigen (MBA) gene sequence. Results: U parvum was identified in 58 of 151 specimens andU. urealyticum in 18 (both were present in 5, and neither werefound in 6). Serovars 3, 1, and 6 were the most commonamong U parvum isolates and subtypes l and 3 were the mostcommon among U urealyticum. Multiple serovars amongclinical isolates were found. Conclusion: This PCR-based typing system could facilitatestudies of the relationship between individual ureaplasmaspecies or subtypes and human diseases.
基金supported by the National Natural Science Foundation of China(21890744,22104032)the National Key R&D Program of China(2019YFA0210100)+1 种基金the China Postdoctoral Science Foundation(2020 M672470)the National Postdoctoral Program for Innovative Talents(BX2020118).
文摘Molecular subtyping of cancer can greatly help to understand the development of disease and predict tumor behavior.Exploring detection methods for precise subtyping is appealing to prognosis and personalized therapy.During the past decades,DNA-based biosensors have exhibited great potential in cancer diagnosis due to their structural programmability and functional diversity.Despite the encouraging progress that has been made,there remains an issue in improving the accuracy and sensitivity of cancer subtyping due to the complex process of disease,especially in preclinical or clinical applications.To accelerate the development of DNA sensors in the identification of cancer subtypes,in this review,we summarized their advances in molecular subtyping by analyzing the heterogeneity in categories and levels of biomarkers between cancer subtypes.The strategies toward genomic and proteomic heterogeneity in cells or on the cell surface,as well as the cancer excretions including extracellular vesicles(EVs)and microRNA(miRNAs)in serum,are summarized.Current challenges and the opportunities of DNA-based sensors in this field are also discussed.
文摘Objective To analyze the value of multi-slice spiral CT ( SCT) scan in staging and subtyping of renal cell carcinoma ( RCC) . Methods The preoperative kidney SCT data and postoperative pathology results of 64 patients with RCC were retrospectively analyzed. The pa-
文摘The prevalence of type 2 diabetes mellitus(T2DM)is increasing rapidly worldwide.Because of the limited success of generic interventions,the focus of the disease study has shifted toward personalized strategies,particularly in the early stages of the disease.Traditional Chinese medicine(TCM)is based on a systems view combined with personalized strategies and has improved our knowledge of personalized diagnostics.From a systems biology perspective,the understanding of personalized diagnostics can be improved to yield a biochemical basis for such strategies;for example,metabolomics can be used in combination with other system-based diagnostic methods such as ultra-weak photon emission(UPE).In this study,we investigated the feasibility of using plasma metabolomics obtained from 44 pre-T2DM subjects to stratify the following TCM-based subtypes:Qi-Yin deficiency,Qi-Yin deficiency with dampness,and Qi-Yin deficiency with stagnation.We studied the relationship between plasma metabolomics and UPE with respect to TCM-based subtyping in order to obtain biochemical information for further interpreting disease subtypes.Principal component analysis of plasma metabolites revealed differences among the TCM-based pre-T2DM subtypes.Relatively high levels of lipids(e.g.,cholesterol esters and triglycerides)were important discriminators of two of the three subtypes and may be associated with a higher risk of cardiovascular disease.Plasma metabolomics data indicate that the lipid profile is an essential component captured by UPE with respect to stratifying subtypes of T2DM.The results suggest that metabolic differences exist among different TCM-based subtypes of pre-T2DM,and profiling plasma metabolites can be used to discriminate among these subtypes.Plasma metabolomics thus provides biochemical insights into system-based UPE measurements.
基金financially supported by the Scientific Project Unit of Erzincan University(Project No:SAG-A-240215-0128).
文摘Objective:To investigate Blastocystis’etiologic role and association with gastrointestinal symptomatology in acute and chronic urticaria patients and to identify Blastocystis subtypes responsible for urticaria.Methods:The study included urticaria patients and healthy individuals that presented to our polyclinic between June 2015 and May 2017.The participants were assigned into Group栺(137 patients),subdivided into acute(72)and chronic urticaria patients(65),and Group栻(129 control individuals).Blastocystis presence was investigated by native-Lugol examination,trichrome staining,PCR using sequence tagged site primers,and DNA sequencing analysis.The phylogenetic tree was constructed.Results:The native-Lugol and trichrome staining methods revealed that 16 patients(16/133,12.0%)had Blastocystis-positive stool samples,of which seven samples(7/133,5.3%)belonged acute and nine(9/133,6.8%)to chronic urticaria patients.Concerning Blastocystis subtypes,of the acute urticaria patients,three had subtype 1(ST1),one had ST2,and three had ST3.Of the chronic urticaria patients,one had ST1 and eight had ST3.Blastocystis positivity was detected in two control individuals(2/123,1.6%),both being ST3.All subtypes identified by PCR were confirmed by the sequencing analysis.The acute and chronic urticaria groups showed no statistically significant differences for Blastocystis positivity(P=0.60)and subtype distribution(P=0.15).A statistically significant difference was found between the urticaria patients and the controls for Blastocystis positivity(P<0.01),but not for subtype distribution(P=0.67)or for Blastocystis presence and gastrointestinal complaints.Conclusions:This study on Blastocystis subtype distribution among Turkish urticaria patients showed results consistent with the literature.It was concluded that Blastocystis should be kept in mind in patients with urticaria.
文摘Background: Breast cancer is a genetically and clinically heterogeneous disease with multiple subtypes. The classification of these subtypes has evolved over the years. The most common and widely accepted classification of breast cancer is from an immunohistochemical perspective, based on the expression of the following hormone receptors: Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor (HER2). Accordingly, the following four subtypes of breast cancer are widely recognized—Luminal A, Luminal B, HER2 Enriched and Triple Negative. Breast cancer management approaches include surgery, chemotherapy, radiotherapy and targeted hormone therapy necessitated by molecular subtyping. Aims: This study aimed to determine the level of adherence to breast cancer molecular subtyping among women with breast cancer attending tertiary health facilities in Imo State. Methodology: Immunohistochemistry reports of women with breast cancer attending tertiary health facilities in Imo State were retrieved from patient’s case files. Tissue blocks were also retrieved from tissue block archives of both hospitals for women who did not take up immunohistochemistry services after their initial diagnosis and also those whose immunohistochemistry reports were not found in their case files. Results: Among the 121 women that participated in the study, there were in all 74 (61.2%) had molecular subtyping of their tumour blocks. Up to 45 (37.2%) did not go for molecular subtyping of their tumour blocks while 2 (1.7%) were not sure whether they had or not. Conclusion: It, therefore, depicts that the rate of uptake was found as 61.2% among the participants and there is a need to create more awareness of the importance of molecular subtyping, which necessitates the use of targeted hormone therapy.
基金The study design,data collection,data analysis,manuscript preparation,and publication decisions of this work were supported by the Science and Technology Program of Zhejiang Province Traditional Chinese Medicine(2023ZL056,2023ZL409)the Foundation Project of Zhejiang Chinese Medical University(2022JKZKTS26,2022JKJNTZ16,2022JKJNTZ23).
文摘Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may affect APOD expression.Therefore,this paper aims to investigate the significance of APOD expression and APOD DNA methylation in breast cancer.Methods:This study utilized comprehensive bioinformatics analysis of APOD using Gene Expression database of Normal and Tumor tissues 2,UCSC Xena,etc.Clinical and survival information obtained from the The Cancer Genome Atlas and Gene Expression Omnibus datasets were extracted for data mining.Results:The correlation between APOD and breast cancer was examined,along with the connection between APOD DNA methylation and APOD expression.In the The Cancer Genome Atlas cohort,as well as GSE31448 and GSE65194 datasets,APOD expression decreased in breast cancer(P<0.0001).Clinical feature analysis results showed that APOD expression was correlated with the PAM50 subtype,with the lowest expression in the Basal subtype(P<0.0001).High APOD expression is a good prognostic marker for breast cancer(HR=0.71,P=0.037).APOD methylation level was significantly negatively correlated with expression level(R=−0.4770,P<0.001),and cg15231202,cg23720929,and cg05624196 were important regulatory targets.High APOD expression was associated with higher metabolism and extracellular matrix scores.Conclusion:APOD is an independent prognostic marker for breast cancer and is regulated by DNA methylation to modulate mRNA expression.
基金Supported by the National Key Research and Development Plan:Regulatory Pathways and Mechanisms of Conception and Governor Vessels Surface Stimulation in the Treatment of “Uterus and Brain” Disorders (No. 2022YFC3500405)Taishan Scholar Youth Project of Shandong Province (No. tsqn202306188)+3 种基金the National Natural Science Foundation of China:Epigenetic Regulation of Vascular Neural Unit Function by Vascular Endothelial Histone Deacetylase:a New Antidepressant Application and Mechanism of Huangqi Guizhi Wuwu Decoction (No. 82274128)the National Natural Science Foundation of China:Study on the Anti-depression Mechanism of Electroacupuncture based on the Regulation of Biological Clock Gene in Prefrontal Cortex (No. 81973948)Joint Fund of Shandong Provincial Natural Science Foundation:High-Throughput Screening and Key Target Validation of Traditional Chinese Medicine Blood-Activating and Stasis-Resolving Components using a Vascular Microenvironment Simulation Chip (No. ZR2021LZY020)Student Research Training Program of Shandong University of Traditional Chinese Medicine:the Therapeutic Mechanism of Huangqi Guizhi Wuwu Decoction on Chronic Unpredictable Mild Stress Model Mice Based on the Endothelial Nitric Oxide Synthase-Nitric oxide Pathway Research of Vascular Endothelial Eells (No. 202210441008)
文摘OBJECTIVE:To research the subtyping and treatment of depression by leveraging studying on extensive Traditional Chinese Medicine(TCM)experiences through artificial intelligence(AI).METHODS:We retrieved depression-related literature published from inception to April 2023 from databases.From these sources,we extracted symptoms,signs,and prescriptions associated with depression.By utilizing the tree number system in the medical subject headings(MeSH),we established a hierarchical relationship matrix for symptoms/signs,as well as depression sample fingerprints.Using an unsupervised clustering algorithm,we constructed a machine learning model for classifying depression patients.Furthermore,we conducted an analysis of medication rules for each depression cluster.RESULTS:We created a My Structured Query Language(MySQL)database containing datasets of depression-symptoms/signs and depression-herbs,through mining 3522 published clinical literatures on TCM diagnosis and treatment for depression.We established hierarchical relationships among symptoms/signs of depression patients.Our unsupervised clustering analysis revealed that depression patients could be classified into 9 subtypes,with each subtype corresponding to a specific treatment prescription.Notably,one of the depression subtypes was consistently treated by Qi-tonifying formulas and herbs.This finding was further supported by data from Qi-deficiency patients,as there was a high similarity in the top symptoms/signs shared between this subtype and Qi-deficiency diagnosed by TCM.CONCLUSIONS:This study identified the subtypes and TCM treatment of depression by using machine learning and text mining.
基金supported by the National Natural Science Foundation of China(82102018,62333002,T2425027,and 82327809)Data collection and sharing for this project were supported by the National Natural Science Foundation of China(61633018,81571062,81471120,and 81901101)+30 种基金Data collection and sharing for this project were funded by the ADNI(National Institutes of Health Grant U01 AG024904)the Department of Defense ADNI(award number W81XWH-12-2-0012).The ADNI is funded by the National Institute on Aging,the National Institute of Biomedical Imaging and Bioengineering,and through generous contributions from the following:AbbVie,Alzheimer’s AssociationAlzheimer’s Drug Discovery FoundationAraclon BiotechBioClinica,Inc.BiogenBristol-Myers Squibb Co.CereSpir,Inc.CogstateEisai Inc.Elan Pharmaceuticals,Inc.Eli Lilly and Co.EuroImmunF.Hoffmann-La Roche Ltd and its affiliated company Genentech,Inc.FujirebioG.E.HealthcareIXICO Ltd.Janssen Alzheimer Immunotherapy Research&Development,LLC.Johnson&Johnson Pharmaceutical Research&Development LLC.LumosityLundbeckMerck&Co.,Inc.Meso Scale Diagnostics,LLC.NeuroRx ResearchNeurotrack TechnologiesNovartis Pharmaceuticals Corp.Pfizer Inc.Piramal ImagingServierTakeda Pharmaceutical Co.and Transition Therapeutics.The Canadian Institutes of Health Research provides funds to support ADNI clinical sites in Canada.Private sector contributions are facilitated by the Foundation for the National Institutes of Health(www.fnih.org).The grantee organization was the Northern California Institute for Research and Education,and the study was coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California.ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
文摘Dear Editor,Growing clinical evidence shows that brain disorders are heterogeneous in phenotype,genetics,and neuropathology[1].Diagnosis and treatment tend to be affected by symptom presentation and the heterogeneity of pathology,potentially hindering clinical trials in the development of medical treatment.Brain-based subtyping studies utilize magnetic resonance imaging(MRI)and data-driven methods to discover the subtypes of diseases,providing a new perspective on disease heterogeneity.
基金National Natural Science Foundation of China(82173332).
文摘During the process of carcinogenesis and tumor progression,various molecular alternations occur in different omics levels.In recent years,multiomics approaches including genomics,epigenetics,transcriptomics,proteomics,metabolomics,single-cell omics,and spatial omics have been applied in mapping diverse omics profiles of cancers.The development of high-throughput technologies such as sequencing and mass spectrometry has revealed different omics levels of tumor cells or tissues separately.While focusing on a single omics level results in a lack of accuracy,joining multiple omics approaches together undoubtedly benefits accurate molecular subtyping and precision medicine for cancer patients.With the deepening of tumor research in recent years,taking pathological classification as the only criterion of diagnosis and predicting prognosis and treatment response is found to be not accurate enough.Therefore,identifying precise molecular subtypes by exploring the molecular alternations during tumor occurrence and development is of vital importance.The review provides an overview of the advanced technologies and recent progress in multiomics applied in cancer molecular subtyping and detailedly explains the application of multiomics in identifying cancer driver genes and metastasis-related genes,exploring tumor microenvironment,and selecting liquid biopsy biomarkers and potential therapeutic targets.
基金suppor ted by the US Depar tment of Defense Congressionally Directed Medical Research Program (CDMRP)awards (http://cdmrp.army.mil/) W81XWH-16-1-0632 (Craddock PI),W81XWH-16-1-0552 (Craddock PI),W81XWH-18-1-0549 (Sullivan PI),W81XWH-13-2-0072 (Sullivan PI),and W81XWH-09-2-0071 (Klimas PI)a Veterans Affairs Merit Award (4987.69) to Dr.Nancy Klimas。
文摘Background:One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction,skin rashes,musculoskeletal discomfort,and fatigue.This symptom cluster is now referred to as Gulf War Illness(GWI).As the underlying mechanisms of GWI have yet to be fully elucidated,diagnosis and treatment are based on symptomatic presentation.One confounding factor tied to the illness is the high presence of post-traumatic stress disorder(PTSD).Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction.As such,this research endeavor aimed to provide insight into the complex relationship between GWI symptoms,cytokine presence,and immune cell populations to pinpoint the impact of PTSD on these measures in GWI.Methods:Symptom measures were gathered through the Multidimensional fatigue inventory(MFI)and 36-item short form health survey(SF-36)scales and biological measures were obtained through cytokine&cytometry analysis.Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders(DSM)-5,into GWI with high probability of PTSD symptoms(GWIH)and GWI with low probability of PTSD symptoms(GWIL).Data was analyzed using analysis of variance(ANOVA)statistical analysis along with correlation graph analysis.We mapped correlations between immune cells and cytokine signaling measures,hormones and GWI symptom measures to identify patterns in regulation between the GWIH,GWIL,and healthy control groups.Results:GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both healthy control(HC)and the GWIL subgroup.Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity(ANOVA F=4.7,P=0.01)indicating its potential usage as a biomarker for general GWI from control.While the unique identification of GWI with PTSD symptoms was less clear,the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge(ANOVA F>3.75,P<0.03).Additional differences in natural killer(NK)cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms.Conclusions:We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.
基金supported by the Guangzhou Municipal Basic Research Program Jointly Funded by City,University,and Enterprise Special Project(2024A03J0907)the Natural Science Foundation of Guangdong Province(2024A1515013201)+1 种基金the National Natural Science Foundation of China(82203720,82203188,82002682,81972731,81773026,81972383)the Science and Technology Project of Zhongshan Municipality(No.2024B1032).
文摘Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predict BCa molecular subtypes.Method:We developed a predictive model for BCa molecular subtypes using machine learning(ML)and pathomics derived from Hematoxylin-Eosin stained pathological slides.A cohort of 353 patients from TCGA was employed,and image features were extracted for analysis.Pathomic signatures were constructed using the LASSO Cox regression algorithm,and a pathomic-clinical nomogram was developed and validated in training and testing cohorts.Results:Seventy distinct image features were identified from 150 pathomic signatures.The model demonstrated robust predictive ability,with AUCs of 0.833 and 0.822 in the training and validation cohorts,respectively.The addition of pathomic score,N stage,and M stage improved the model’s discrimination,achieving AUCs of 0.877 and 0.794 in the training and validation cohorts.Limitations include the lack of an external validation cohort.Conclusion:Our ML-based pathomics model shows promise in predicting BCa molecular subtypes and has the potential to enhance prognosis prediction and inform treatment strategies,marking a significant step towards precision medicine for BCa.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82172635,82272686,and 82203628)Natural Science Foundation of Tianjin(Grant No.23JCZDJC00200)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-010A).
文摘Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 is insufficient to predict therapeutic outcomes3,4.A recently identified vulnerability in SCLC involves the dysregulation of nuclear-cytoplasmic transport,particularly through exportin 1(XPO1)5-7.
基金This work was supported in part by the grant from the National Science and Technology Major Project of China(No.2017ZX10203205)the Science Foundation of Zhejiang province(LQ18H160006).
文摘Hepatocellular carcinoma(HCC)is one of the most prevalent and fatal digestive tumors.Treatment for this disease has been constraint by heterogeneity of this group of tumors,which has greatly limited the progress in personalized therapy.Although existing studies have revealed the genetic and epigenetic blueprints that drive HCCs,many of the molecular mechanisms that lead to HCCs remain elusive.Recent advances in techniques for studying functional genomics,such as genome sequencing and transcriptomic analyses,have led to the discovery of molecular mechanisms that participate in the initiation and evolution of HCC.Integrative multi-omics analyses have identified several molecular subtypes of HCC associated with specific molecular characteristics and clinical outcomes.Deciphering similar molecular features among highly heterogeneous HCC patients is a prerequisite to implementation of personalized therapeutics.This review summarizes the current research progresses in precision therapy on the backbone of molecular subtypes of HCC.
