Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help ...Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.展开更多
Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted ...Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.展开更多
BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and sui...BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and suitable subpopu-lations for mRNA vaccination.METHODS Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas.Genes with somatic mutations and copy number variations were identified by cBioPortal analysis.The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis.The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells(APCs).Tumor-associated antigens were overexpressed in tumors and associated with prognosis,genomic alterations,and APC infiltration.A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes.The weighted gene coexpression network analysis(WGCNA)was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines.immune subtypes showed distinct cellular and clinical characteristics.The IS1 and IS3 immune subtypes were immunologically“cold”.The IS2 and IS4 immune subtypes were immunologically“hot”,and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes.IS1-related modules were identified with the WGCNA algorithm.Ultimately,five hub genes(RBP4,KNG1,METTL7A,F12,and ABAT)were identified,and they might be potential biomarkers for mRNA vaccines.CONCLUSION AURKA,CCNB1,CDC25C,CDK1,TRIP13,PES1,MCM3,PPM1G,NEK2,KIF2C,PTTG1,KPNA2,and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development.The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination.RBP4,KNG1,METTL7A,F12,and ABAT are potential biomarkers for mRNA vaccines.展开更多
BACKGROUND Synchronous colorectal carcinomas(SCRC)are two or more primary colorectal carcinomas identified simultaneously or within 6 mo of the initial presentation in a single patient.Their incidence is low and the n...BACKGROUND Synchronous colorectal carcinomas(SCRC)are two or more primary colorectal carcinomas identified simultaneously or within 6 mo of the initial presentation in a single patient.Their incidence is low and the number of pathological types of SCRC is usually no more than two.It is very unusual that the pathological findings of a patient with SCRC show more than two different pathological subtypes.Here,we report a rare case of SCRC with three pathological subtypes.CASE SUMMARY A 75-year-old woman who had no previous medical history or family history was admitted to the hospital because of intermittent hematochezia for more than a month.Colonoscopy displayed an irregularly shaped neoplasm of the rectum,a tumor-like lesion causing intestinal stenosis in the descending colon,and a polypoidal neoplasm in the ileocecum.Subsequently,she underwent total colectomy,abdominoperineal resection for rectal cancer,and ileostomy.After operation,the pathological report showed three pathological subtypes including well-differentiated adenocarcinoma of the ascending colon,moderately differen-tiated adenocarcinoma of the descending colon,and mucinous adenocarcinoma of the rectum.She is now recovering well and continues to be closely monitored during follow-up.CONCLUSION Preoperative colonoscopy examination,imaging examination,and extensive intraoperative exploration play important roles in reducing the number of missed lesions.展开更多
BACKGROUND Acute myeloid leukemia(AML)is one of the most common types of leukemia in adults.However,AML is relatively rare in the population overall,accounting for only about 1 percent of all cancers.Treatment for AML...BACKGROUND Acute myeloid leukemia(AML)is one of the most common types of leukemia in adults.However,AML is relatively rare in the population overall,accounting for only about 1 percent of all cancers.Treatment for AML can be very effective for some patients,yet it leaves others with serious and even life-threatening side effects.Chemotherapy is still the primary treatment for most AML,but over time,leukemia cells become resistant to chemotherapy drugs.In addition,stem cell transplantation,targeted therapy,and immunotherapy are currently available.At the same time,with the progression of the disease,the patient may have corresponding complications,such as coagulation dysfunction,anemia,granulocytopenia,and repeated infection,so transfusion supportive therapy will be involved in the overall treatment regime.To date,few articles have reported on blood transfusion treatment options for patients with ABO subtypes AML-M2.Blood transfusion therapy is an important supportive treatment for AML-M2,and accurate determination of patients'blood type is one of the most important steps in the treatment process.In this study,we explored blood typing and supportive treatment strategies for a patient with A2 subtype AML-M2 to provide the basis for treatment for all patients.CASE SUMMARY In order to determine the blood type of the patient,serological and molecular biological methods were used for reference tests,and the genetic background was studied to determine the patient's final blood type and select the appropriate blood products for infusion treatment.According to the results obtained by serological and molecular biological methods,the blood type of the patient was A2 subtype;the genotype was A02/001;the irregular antibody screening was negative,and anti-A1 was found in the plasma.According to the overall treatment plan,active anti-infection,elevated cells,component blood transfusion support,and other rescue and supportive treatments were given,and the patient successfully passed the stage of myelosuppression after chemotherapy.Re-examination of bone marrow smears showed that AL was in complete remission of bone marrow signs,and minimal residual leukemia lesions suggested no cells with obvious abnormal immunophenotype(residual leukemia cells<10-4).CONCLUSION The infusion of patients with A2 subtype AML-M2 with A irradiated platelets and O washing red blood cells can meet the needs of clinical treatment.展开更多
BACKGROUND Colorectal cancer is a complex disease with high mortality rates.Over time,the treatment of metastatic colorectal cancer(mCRC)has gradually improved due to the development of modern chemotherapy and targete...BACKGROUND Colorectal cancer is a complex disease with high mortality rates.Over time,the treatment of metastatic colorectal cancer(mCRC)has gradually improved due to the development of modern chemotherapy and targeted therapy regimens.However,due to the inherent heterogeneity of this condition,identifying reliable predictive biomarkers for targeted therapies remains challenging.A recent promising classification system—the consensus molecular subtype(CMS)system—offers the potential to categorize mCRC patients based on their unique biological and molecular characteristics.Four distinct CMS categories have been defined:immune(CMS1),canonical(CMS2),metabolic(CMS3),and mesenchymal(CMS4).Nevertheless,there is currently no standardized protocol for accurately classifying patients into CMS categories.To address this challenge,reverse transcription polymerase chain reaction(RT-qPCR)and next-generation genomic sequencing(NGS)techniques may hold promise for precisely classifying mCRC patients into their CMSs.AIM To investigate if mCRC patients can be classified into CMS categories using a standardized molecular biology workflow.METHODS This observational study was conducted at the University of Chile Clinical Hospital and included patients with unresectable mCRC who were undergoing systemic treatment with chemotherapy and/or targeted therapy.Molecular biology techniques were employed to analyse primary tumour samples from these patients.RT-qPCR was utilized to assess the expression of genes associated with fibrosis(TGF-βandβ-catenin)and cell growth pathways(c-MYC).NGS using a 25-gene panel(TumorSec)was performed to identify specific genomic mutations.The patients were then classified into one of the four CMS categories according to the clinical consensus of a Tumour Board.Informed consent was obtained from all the patients prior to their participation in this study.All techniques were conducted at University of Chile.RESULTS Twenty-six patients were studied with the techniques and then evaluated by the Tumour Board to determine the specific CMS.Among them,23%(n=6),19%(n=5),31%(n=8),and 19%(n=5)were classified as CMS1,CMS2,CMS3,and CMS4,respectively.Additionally,8%of patients(n=2)could not be classified into any of the four CMS categories.The median overall survival of the total sample was 28 mo,and for CMS1,CMS2,CMS3 and CMS4 it was 11,20,30 and 45 mo respectively,with no statistically significant differences between groups.CONCLUSION A molecular biology workflow and clinical consensus analysis can be used to accurately classify mCRC patients.This classification process,which divides patients into the four CMS categories,holds significant potential for improving research strategies and targeted therapies tailored to the specific characteristics of mCRC.展开更多
Recent studies demonstrated that bladder cancers can be grouped into basal and luminal molecular subtypes that possess distinct biological and clinical characteristics.Basal bladder cancers express biomarkers characte...Recent studies demonstrated that bladder cancers can be grouped into basal and luminal molecular subtypes that possess distinct biological and clinical characteristics.Basal bladder cancers express biomarkers characteristic of cancer stem cells and epithelial-tomesenchymal transition(EMT).Patients with basal cancers tend have more advanced stage and metastatic disease at presentation.In preclinical models basal human orthotopic xenografts are also more metastatic than luminal xenografts are,and they metastasize via an EMT-dependent mechanism.However,preclinical and clinical data suggest that basal cancers are also more sensitive to neoadjuvant chemotherapy(NAC),such that most patients with basal cancers who are aggressively managed with NAC have excellent outcomes.Importantly,luminal bladder cancers can also progress to become invasive and metastatic,but they appear to do so via mechanisms that are much less dependent on EMT and may involve help from stromal cells,particularly cancer-associated fibroblasts(CAFs).Although patients with luminal cancers do not appear to derive much clinical benefit from NAC,the luminal tumors that are infiltrated with stromal cells appear to be sensitive to anti-PDL1 antibodies and possibly other immune checkpoint inhibitors.Therefore,neoadjuvant and/or adjuvant immunotherapy may be the most effective approach in treating patients with advanced or metastatic infiltrated luminal bladder cancers.展开更多
Background: Stage at diagnosis and molecular subtype are important clinical factors associated with breast cancer patient survival. However, subgroup survival data from a large study sample are limited in China.To est...Background: Stage at diagnosis and molecular subtype are important clinical factors associated with breast cancer patient survival. However, subgroup survival data from a large study sample are limited in China.To estimate the survival differences among patients with different stages and various subtypes of breast cancer, we conducted a hospital-based multi-center study on breast cancer in Beijing, China.Methods: All resident patients diagnosed with primary, invasive breast cancer between January 1,2006 and December 31,2010 from four selected hospitals in Beijing were included and followed up until December 31,2015. Hospitalbased data of stage at diagnosis, hormone receptor status, and selected clinical characteristics, including body mass index(BMI), menopausal status, histological grade, and histological type, were collected from the medical records of the study subjects. Overall survival(OS) and cancer-specific survival(CSS) were estimated. Cox proportional hazards models were employed to evaluate the associations of stage at diagnosis and molecular subtype with patient survival.Results: The 5-year OS and CSS rates for all patients were 89.4% and 90.3%. Survival varied by stage and molecular subtype. The 5-year OS rates for patients with stage I, Ⅱ, Ⅲ, and IV diseases were 96.5%, 91.6%, 74.8%, and 40.7%,respectively, and the corresponding estimates of 5-year CSS rates were 97.1%, 92.6%, 75.6%, and 42.7%, respectively.The 5-year OS rates for patients with luminal A, luminal B, HER2, and triple-negative subtypes of breast cancer were92.6%, 88.4%, 83.6%, and 82.9%, respectively, and the corresponding estimates of 5-year CSS rates were 93.2%, 89.1 %,85.4%, and 83.5%, respectively. Multivariate analysis showed that stage at diagnosis and molecular subtype were important prognostic factors for breast cancer.Conclusions: Survival of breast cancer patients varied significantly by stage and molecular subtype. Cancer screening is encouraged for the early detection and early diagnosis of breast cancer. More advanced therapies and health care policies are needed on HER2 and triple-negative subtypes.展开更多
Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. ...Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.展开更多
Objective Tick-borne encephalitis virus(TBEV) is an emerging pathogen in Europe and North Asia that causes tick-borne encephalitis(TBE). A simple, rapid method for detecting TBEV RNA is needed to control this disease....Objective Tick-borne encephalitis virus(TBEV) is an emerging pathogen in Europe and North Asia that causes tick-borne encephalitis(TBE). A simple, rapid method for detecting TBEV RNA is needed to control this disease. Methods A reverse-transcription recombinase-aided amplification(RT-RAA) assay was developed. This assay can be completed in one closed tube at 39℃ within 30 minutes. The sensitivity and specificity of RT-RAA were validated using non-infectious synthetic RNA representing a fragment of the NS5 region of the wild-type(WT) TBEV genome and the Senzhang strain. Additionally, 10 batches of tick samples were used to evaluate the performance of the RT-RAA assay. Results The analytical limit of detection of the assay was 20 copies per reaction of the TBEV synthetic transcript and 3 plaque-forming units(pfu) per reaction of TBEV titers. With the specific assay, no signal due to other arboviruses was observed. Of the 10 batches of tick samples obtained from the Changbai Mountains of China, three were TBEV-positive, which was consistent with the results of the quantitative real-time PCR assay. Conclusion A rapid, highly sensitive, specific, and easy-to-use method was developed for the detection of the TBEV Far-Eastern subtype.展开更多
AIM To detect human papilloma virus(HPV) presence and to characterize cellular immune response in breast cancer patients. METHODS A total of 74 women were included, of which 48 samples were from patients diagnosed wit...AIM To detect human papilloma virus(HPV) presence and to characterize cellular immune response in breast cancer patients. METHODS A total of 74 women were included, of which 48 samples were from patients diagnosed with breast cancer and 26 patients with benign pathology of the breast. Molecular subtype classification was performed based on the immunohistochemical reports of the tumor piece. HPV genome detection and genotyping from fresh breast biopsies was performed using the INNO-LIPA HPV Genotyping Extra test(Innogenetics, Ghent, Belgium). CD3+, CD4+, CD8+ and natural killer(NK)+ cells levels from peripheral blood samples from patients with breast cancer and benign pathology were measured by flow cytometry. RESULTS Luminal A was the most frequent breast cancer molecular subtype(33.33%). HPV was detected in 25% of the breast cancer patients, and genotype 18 was the most frequent in the studied population. The mean of CD3+, CD4+ and CD8+ subpopulations were decreased in patients with breast cancer, in relation to those with benign pathology, with a statistically significant difference in CD8+ values(P = 0.048). The mean of NK+ cells was increased in the benign pathology group. The average level of CD3+, CD4+, CD8+ and NK+ cells decreased as the disease progressed. HER2+ and Luminal B HER2+ tumors had the lowest counts of cell subsets. HPV breast cancer patients had elevated counts of cellular subsets. CONCLUSION Determining level changes in cellular subsets in breast cancer patients is a useful tool to evaluate treatment response.展开更多
The limited molecular classifications and disease signatures of osteoarthritis(OA)impede the development of prediagnosis and targeted therapeutics for OA patients.To classify and understand the subtypes of OA,we colle...The limited molecular classifications and disease signatures of osteoarthritis(OA)impede the development of prediagnosis and targeted therapeutics for OA patients.To classify and understand the subtypes of OA,we collected three types of tissue including cartilage,subchondral bone,and synovium from multiple clinical centers and constructed an extensive transcriptome atlas of OA patients.By applying unsupervised clustering analysis to the cartilage transcriptome,OA patients were classified into four subtypes with distinct molecular signatures:a glycosaminoglycan metabolic disorder subtype(C1),a collagen metabolic disorder subtype(C2),an activated sensory neuron subtype(C3),and an inflammation subtype(C4).Through ligand-receptor crosstalk analysis of the three knee tissue types,we linked molecular functions with the clinical symptoms of different OA subtypes.For example,the Gene Ontology functional term of vasculature development was enriched in the subchondral bone-cartilage crosstalk of C2 and the cartilage-subchondral bone crosstalk of C4,which might lead to severe osteophytes in C2 patients and apparent joint space narrowing in C4 patients.Based on the marker genes of the four OA subtypes identified in this study,we modeled OA subtypes with two independent published RNA-seq datasets through random forest classification.The findings of this work contradicted traditional OA diagnosis by medical imaging and revealed distinct molecular subtypes in knee OA patients,which may allow for precise diagnosis and treatment of OA.展开更多
To investigate the epizootic of swine influenza virus(SIV),60 nasal swabs were collected from a clinical cases of pig farm in Tai’an City,Shandong Province of China in April 2017.SIV was isolated by inoculating into ...To investigate the epizootic of swine influenza virus(SIV),60 nasal swabs were collected from a clinical cases of pig farm in Tai’an City,Shandong Province of China in April 2017.SIV was isolated by inoculating into 10-day-old Special Pathogen Free embryonated eggs and the whole genome was sequenced.An H1N1 subtype SIV was isolated and designated as A/swine/Shandong/TA04/2017(H1N1).Phylogenetic analysis showed that apart from the polymerase A(PA) fragment belonging to the 2009 pandemic H1N1 branch,seven genome segments belonged to avian-like H1N1 influenza virus lineage.The cleavage site sequence of the hemagglutinin(HA) protein was PSIQSR↓G,which is a typical molecular biological characteristic.Five potential N-glycosylation sites(N14,N26,N277,N484 and N543) were found in the HA gene.To further investigate the epidemiology of SIV in this farm,the 995 serum samples were assessed with EAH1N1 2009 pandemic H1N1 and H3 N2 antigens.The results showed that the total positive rate was 65.43%.The positive rates of single virus infection detected by EAH1N1,2009 pdmH1N1 and H3 N2 for serum HI(Hemagglutination inhibition) were 48.35,30.85 and 7.47%,respectively.The results showed that SIV in Shandong Province has been reassorted in some segments and the SIV-positive rate was high on the SIV outbreak farm.These data provide evidence of an epizootic of SIV.展开更多
Intrahepatic cholangiocarcinoma is macroscopically classified into three subtypes, mass-forming-type, periductal infiltrating-type, and intraductal growth-type. Each subtype should be preoperatively differentiated to ...Intrahepatic cholangiocarcinoma is macroscopically classified into three subtypes, mass-forming-type, periductal infiltrating-type, and intraductal growth-type. Each subtype should be preoperatively differentiated to perform the valid surgical resection. Recent researches have revealed the clinical, radiologic, pathobiological characteristics of each subtype. We reviewed recently published studies covering various aspects of intrahepatic cholangiocarcinoma(ICC), focusing especially on the macroscopic subtypes and stem cell features to better understand the pathophysiology of ICC and to establish the valid therapeutic strategy.展开更多
BACKGROUND Carcinoma of the ampulla of Vater is an uncommon ampullo-pancreatobiliary neoplasm,and the most common histological type is adenocarcinoma with a tubular growth pattern.Invasive micropapillary carcinoma(IMP...BACKGROUND Carcinoma of the ampulla of Vater is an uncommon ampullo-pancreatobiliary neoplasm,and the most common histological type is adenocarcinoma with a tubular growth pattern.Invasive micropapillary carcinoma(IMPC)is an aggressive variant of adenocarcinoma in several organs that is associated with lymph node metastasis and poor prognosis.IMPC was first described as a histological subtype of breast cancer;however,IMPC of the ampulla of Vater is extremely rare,with only three articles reported in the English literature.CASE SUMMARY We have reported a case of IMPC of the ampulla of Vater in an 80-year-old man.Microscopically,the surface area of the carcinoma was composed of tubulopapillary structures mimicking intra-ampullary papillary-tubular neoplasm,and the deep invasive front area exhibited a pattern of IMPC.The carcinoma showed lymphatic invasion and extensive lymph node metastasis.The immunohistochemical study revealed mixed intestinal and gastric/pancreatobiliary phenotypes.CONCLUSION This rare subtype tumor in the ampulla of Vater showed a histologically mixed phenotype and exhibited aggressive behavior.展开更多
Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and...Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC.展开更多
The brain tumor perivascular niche(PVN),the region in the vicinity of microvessels is a prime location for brain tumor stem-like cells(BTSCs)[1].Tumor microvasculature creates a complex microenvironment consisting of ...The brain tumor perivascular niche(PVN),the region in the vicinity of microvessels is a prime location for brain tumor stem-like cells(BTSCs)[1].Tumor microvasculature creates a complex microenvironment consisting of various cell types,the extracellular matrix,and soluble factors that mediate cell-cell interaction.The brain tumor PVN controls maintenance,expansion,and differentiation of BTSCs via direct cell contact or paracrine signaling cues.BTSCs often receive bidirectional crosstalk from endothelial cells and other cell types in the niche[2].In addition,the perivascular zone may serve as a path for tumor cells to migrate over long distances(3,4)Unlike other solid tumors,glioblastoma multiforme(GBM)cells rarely metastasize to other organs,but they can invade the entire brain by migrating along specific brain tissue structures,such as blood vessels or white matter tracts,leading to high rates of relapse.Despite the success in modeling diffuse brain tumors in both genetically-modified and patient-derived xenograft(PDX)animals,there is an unmet need for an in vitro system that can bridge conventional cell culture and animal models by mimicking not only the anatomy but also the function of the PVN to study the dynamics of BTSCs.In this presentation,I will describe the use of a microvasculature-on-a-chip system as a PVN model to evaluate the dynamics of BTSCs ex vivo from 10 glioblastoma patients [5].We observed that BTSCs preferentially localize in the perivascular zone.Live cell tracking showed that the cells residing in the vicinity of microvessels had the lowest motility,while a fraction of cells on the microvessels unexpectedly possessed the highest motility and migrated over the longest distance.These results indicate that the perivascular zone is a niche for BTSCs,while the microvascular tracks are also a path for long-distance tumor cell migration and invasion.Additionally,the degree of co-localization between tumor cells and microvessels varied significantly across patients.To validate the results from our microvasculature-on-a-chip system,we used single-cell transcriptome sequencing(10 patients and 21,750 single cells in total)to identify the subtype of each tumor cell.The co-localization coefficient was found to correlate positively with proneural(stem-like)or mesenchymal(invasive)but not classical(proliferative)tumor cells.Furthermore,we found that a gene signature profile including PDGFRA correlated strongly with the'homing'of brain tumor cells to the PVN.Our findings demonstrated that ex vivo dynamics of human brain tumor cells in a microvasculature-on-a-chip model can recapitulate in vivo tumor cell dynamics,heterogeneity,and subtypes,representing a new route to the study of human tumor cell biology and uncover patient-specific tumor cell functions.Acknowledgments:We thank Drs.Laura Niklason,Eric Holland,Franziska Michor,and Frank Szulzewsky for scientific discussion.We thank Misha Guy,Vladimir Polejaev,Zhenting Jiang,and Alice Yun for suggestions and help on the simulation computing and SEM/confocal imaging process.This research was supported by the Packard Fellowship for Science and Engineering(R.F.),National Science Foundation CAREER Award CBET-1351443(R.F.),U54 CA193461(R.F.),U54CA209992(Sub-Project ID:7297 to R.F.),R01 NS095817(J.Z.),Yale Cancer Center Co-Pilot Grant(to R.F.).The molds for microfluidic devices were fabricated in the Yale School of Engineering and Applied Science cleanroom.Sequencing was performed at the Yale Center for Genome Analysis(YCGA)facility.Data was analyzed at Yale High Performance Computing(HPC)center.Super resolution confocal imaging was performed at Yale Center for Cellular and Molecular Imaging(CCMI).展开更多
Objective:The aim of the study was to identify specific chemosensitivity drugs for various molecular subtypes of breast tumors in Chinese women,by detecting the expression of drug resistance genes and by using the dru...Objective:The aim of the study was to identify specific chemosensitivity drugs for various molecular subtypes of breast tumors in Chinese women,by detecting the expression of drug resistance genes and by using the drug sensitivity test on different molecular subtypes of breast cancers.Methods:The expression of drug resistance genes including Topo Ⅱ,GST-π,P-gp,LRP,and CD133 were detected with immunohistochemistry in a tissue microarray.Drug sensitivity tests included those for paclitaxel,epirubicin,carboplatin,vinorelbine,and fluorouracil and were conducted on primary cancer tissue cells and cell lines,including the T47 D,BT-474,and MDA-MB-231 cells and human breast cancer xenografts in nude mice.Results:The different drug resistant genes Topo Ⅱ,GST-π,P-gp,and LRP were differentially expressed among different molecular subtypes of breast cancers(P<0.05).Positive expression of CD133 was highest in basal-like breast cancer(P<0.05).Kaplan-Meier survival analysis showed that positive expressions of Topo Ⅱ and CD133 both correlated with shorter disease-free survival(DFS)(P<0.05)and overall survival(P<0.05),and positive expression of LRP correlated only with shorter DFS(P<0.05).BT-474 showed chemosensitivity to paclitaxel and epirubicin,while MDA-MB-231 showed chemosensitivities to paclitaxel,epirubicin,carboplatin,and fluorouracil(T/C≤50%).The basal-like and HER2+breast cancer primary cells showed chemosensitivities to paclitaxel and epirubicin with significant differences compared with luminal breast cancer primary cells(P<0.05).Conclusions:The differential expression of drug resistance genes and the differential chemosensitivities of drugs in different molecular subtype of breast cancers suggested that individual treatment should be given for each type of breast cancer.展开更多
Research the evaporating crystalization process of the magnesium sulfate subtypes brine at high temperature from Dalangtan salt lake in Qinghai province.It was revealed that the salt lake is a typical subtype
H7 avian influenza viruses(AIVs) normally circulated among birds before. From 1996 to 2012, human infections with H7 AIVs(H7 N2, H7 N3, and H7 N7) were reported in Canada, Italy, Mexico, the Netherlands, the United Ki...H7 avian influenza viruses(AIVs) normally circulated among birds before. From 1996 to 2012, human infections with H7 AIVs(H7 N2, H7 N3, and H7 N7) were reported in Canada, Italy, Mexico, the Netherlands, the United Kingdom and the USA. Until March 2013, human infections with H7 N9 AIVs were reported in China. Since then, H7 N9 AIVs have continued to circulate in both humans and birds. Therefore, the detection of antibodies against the H7 subtype of AIVs has become an important topic. In this study, a competitive enzyme-linked immunosorbent assay(cELISA)method for the detection of antibody against H7 AIVs was established. The optimal concentration of antigen coating was 5 μg mL^(-1), serum dilution was 1/10, and enzyme-labeled antibody was 1/3 000. To determine the cut-off value of cELISA, percent inhibition(PI) was determined by using receiver operating characteristic(ROC) curve analysis in 178 AIVs negative samples and 368 AIVs positive serum samples(n=546). When PI was set at 40%, the specificity and sensitivity of cELISA were 99.4 and 98.9%, respectively. This method could detect the antibodies against H7 Nx(N1–N4, N7–N9) AIVs, and showed no reaction with AIVs of H1–H6 and H8–H15 subtypes or common avian viruses such as Newcastle disease virus(NDV), Infectious bronchitis virus(IBV) and Infectious bursal disease virus(IBDV), exhibiting good specificity. This method showed a coincidence rate of 98.56% with hemagglutinin inhibition(HI) test. And the repeatability experiment revealed that the coefficients of variation(CV) of intra-and inter-batch repetition were all less than 12%. The data indicated that the cELISA antibody-detection method established in this study provided a simple and accurate technical support for the detection of a large number of antibody samples of H7-AIV.展开更多
文摘Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.
基金supported by grants from the 2021 Graduate Education Innovation Program Project of Guangxi Zhuang Autonomous Region [YCBZ2021041]the National innovative training program for college students [202100001580]grants from the National Natural Science Foundation of China [NSFC,31860040]。
文摘Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
文摘BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and suitable subpopu-lations for mRNA vaccination.METHODS Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas.Genes with somatic mutations and copy number variations were identified by cBioPortal analysis.The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis.The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells(APCs).Tumor-associated antigens were overexpressed in tumors and associated with prognosis,genomic alterations,and APC infiltration.A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes.The weighted gene coexpression network analysis(WGCNA)was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines.immune subtypes showed distinct cellular and clinical characteristics.The IS1 and IS3 immune subtypes were immunologically“cold”.The IS2 and IS4 immune subtypes were immunologically“hot”,and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes.IS1-related modules were identified with the WGCNA algorithm.Ultimately,five hub genes(RBP4,KNG1,METTL7A,F12,and ABAT)were identified,and they might be potential biomarkers for mRNA vaccines.CONCLUSION AURKA,CCNB1,CDC25C,CDK1,TRIP13,PES1,MCM3,PPM1G,NEK2,KIF2C,PTTG1,KPNA2,and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development.The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination.RBP4,KNG1,METTL7A,F12,and ABAT are potential biomarkers for mRNA vaccines.
文摘BACKGROUND Synchronous colorectal carcinomas(SCRC)are two or more primary colorectal carcinomas identified simultaneously or within 6 mo of the initial presentation in a single patient.Their incidence is low and the number of pathological types of SCRC is usually no more than two.It is very unusual that the pathological findings of a patient with SCRC show more than two different pathological subtypes.Here,we report a rare case of SCRC with three pathological subtypes.CASE SUMMARY A 75-year-old woman who had no previous medical history or family history was admitted to the hospital because of intermittent hematochezia for more than a month.Colonoscopy displayed an irregularly shaped neoplasm of the rectum,a tumor-like lesion causing intestinal stenosis in the descending colon,and a polypoidal neoplasm in the ileocecum.Subsequently,she underwent total colectomy,abdominoperineal resection for rectal cancer,and ileostomy.After operation,the pathological report showed three pathological subtypes including well-differentiated adenocarcinoma of the ascending colon,moderately differen-tiated adenocarcinoma of the descending colon,and mucinous adenocarcinoma of the rectum.She is now recovering well and continues to be closely monitored during follow-up.CONCLUSION Preoperative colonoscopy examination,imaging examination,and extensive intraoperative exploration play important roles in reducing the number of missed lesions.
文摘BACKGROUND Acute myeloid leukemia(AML)is one of the most common types of leukemia in adults.However,AML is relatively rare in the population overall,accounting for only about 1 percent of all cancers.Treatment for AML can be very effective for some patients,yet it leaves others with serious and even life-threatening side effects.Chemotherapy is still the primary treatment for most AML,but over time,leukemia cells become resistant to chemotherapy drugs.In addition,stem cell transplantation,targeted therapy,and immunotherapy are currently available.At the same time,with the progression of the disease,the patient may have corresponding complications,such as coagulation dysfunction,anemia,granulocytopenia,and repeated infection,so transfusion supportive therapy will be involved in the overall treatment regime.To date,few articles have reported on blood transfusion treatment options for patients with ABO subtypes AML-M2.Blood transfusion therapy is an important supportive treatment for AML-M2,and accurate determination of patients'blood type is one of the most important steps in the treatment process.In this study,we explored blood typing and supportive treatment strategies for a patient with A2 subtype AML-M2 to provide the basis for treatment for all patients.CASE SUMMARY In order to determine the blood type of the patient,serological and molecular biological methods were used for reference tests,and the genetic background was studied to determine the patient's final blood type and select the appropriate blood products for infusion treatment.According to the results obtained by serological and molecular biological methods,the blood type of the patient was A2 subtype;the genotype was A02/001;the irregular antibody screening was negative,and anti-A1 was found in the plasma.According to the overall treatment plan,active anti-infection,elevated cells,component blood transfusion support,and other rescue and supportive treatments were given,and the patient successfully passed the stage of myelosuppression after chemotherapy.Re-examination of bone marrow smears showed that AL was in complete remission of bone marrow signs,and minimal residual leukemia lesions suggested no cells with obvious abnormal immunophenotype(residual leukemia cells<10-4).CONCLUSION The infusion of patients with A2 subtype AML-M2 with A irradiated platelets and O washing red blood cells can meet the needs of clinical treatment.
基金Supported by Agencia Nacional de Investigación y Desarrollo de Chile,Fondo Nacional de Investigación en Salud(FONIS),No.SA20I0059.
文摘BACKGROUND Colorectal cancer is a complex disease with high mortality rates.Over time,the treatment of metastatic colorectal cancer(mCRC)has gradually improved due to the development of modern chemotherapy and targeted therapy regimens.However,due to the inherent heterogeneity of this condition,identifying reliable predictive biomarkers for targeted therapies remains challenging.A recent promising classification system—the consensus molecular subtype(CMS)system—offers the potential to categorize mCRC patients based on their unique biological and molecular characteristics.Four distinct CMS categories have been defined:immune(CMS1),canonical(CMS2),metabolic(CMS3),and mesenchymal(CMS4).Nevertheless,there is currently no standardized protocol for accurately classifying patients into CMS categories.To address this challenge,reverse transcription polymerase chain reaction(RT-qPCR)and next-generation genomic sequencing(NGS)techniques may hold promise for precisely classifying mCRC patients into their CMSs.AIM To investigate if mCRC patients can be classified into CMS categories using a standardized molecular biology workflow.METHODS This observational study was conducted at the University of Chile Clinical Hospital and included patients with unresectable mCRC who were undergoing systemic treatment with chemotherapy and/or targeted therapy.Molecular biology techniques were employed to analyse primary tumour samples from these patients.RT-qPCR was utilized to assess the expression of genes associated with fibrosis(TGF-βandβ-catenin)and cell growth pathways(c-MYC).NGS using a 25-gene panel(TumorSec)was performed to identify specific genomic mutations.The patients were then classified into one of the four CMS categories according to the clinical consensus of a Tumour Board.Informed consent was obtained from all the patients prior to their participation in this study.All techniques were conducted at University of Chile.RESULTS Twenty-six patients were studied with the techniques and then evaluated by the Tumour Board to determine the specific CMS.Among them,23%(n=6),19%(n=5),31%(n=8),and 19%(n=5)were classified as CMS1,CMS2,CMS3,and CMS4,respectively.Additionally,8%of patients(n=2)could not be classified into any of the four CMS categories.The median overall survival of the total sample was 28 mo,and for CMS1,CMS2,CMS3 and CMS4 it was 11,20,30 and 45 mo respectively,with no statistically significant differences between groups.CONCLUSION A molecular biology workflow and clinical consensus analysis can be used to accurately classify mCRC patients.This classification process,which divides patients into the four CMS categories,holds significant potential for improving research strategies and targeted therapies tailored to the specific characteristics of mCRC.
文摘Recent studies demonstrated that bladder cancers can be grouped into basal and luminal molecular subtypes that possess distinct biological and clinical characteristics.Basal bladder cancers express biomarkers characteristic of cancer stem cells and epithelial-tomesenchymal transition(EMT).Patients with basal cancers tend have more advanced stage and metastatic disease at presentation.In preclinical models basal human orthotopic xenografts are also more metastatic than luminal xenografts are,and they metastasize via an EMT-dependent mechanism.However,preclinical and clinical data suggest that basal cancers are also more sensitive to neoadjuvant chemotherapy(NAC),such that most patients with basal cancers who are aggressively managed with NAC have excellent outcomes.Importantly,luminal bladder cancers can also progress to become invasive and metastatic,but they appear to do so via mechanisms that are much less dependent on EMT and may involve help from stromal cells,particularly cancer-associated fibroblasts(CAFs).Although patients with luminal cancers do not appear to derive much clinical benefit from NAC,the luminal tumors that are infiltrated with stromal cells appear to be sensitive to anti-PDL1 antibodies and possibly other immune checkpoint inhibitors.Therefore,neoadjuvant and/or adjuvant immunotherapy may be the most effective approach in treating patients with advanced or metastatic infiltrated luminal bladder cancers.
基金supported by the Beijing Natural Science Foundation (No. 7142139)the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2016-12M-2-004)+1 种基金the PUMC Youth Fund/Fundamental Research Funds for the Central Universities (No. 3332016033)the National Key Research Program of China (No. 2016YFC1302502)
文摘Background: Stage at diagnosis and molecular subtype are important clinical factors associated with breast cancer patient survival. However, subgroup survival data from a large study sample are limited in China.To estimate the survival differences among patients with different stages and various subtypes of breast cancer, we conducted a hospital-based multi-center study on breast cancer in Beijing, China.Methods: All resident patients diagnosed with primary, invasive breast cancer between January 1,2006 and December 31,2010 from four selected hospitals in Beijing were included and followed up until December 31,2015. Hospitalbased data of stage at diagnosis, hormone receptor status, and selected clinical characteristics, including body mass index(BMI), menopausal status, histological grade, and histological type, were collected from the medical records of the study subjects. Overall survival(OS) and cancer-specific survival(CSS) were estimated. Cox proportional hazards models were employed to evaluate the associations of stage at diagnosis and molecular subtype with patient survival.Results: The 5-year OS and CSS rates for all patients were 89.4% and 90.3%. Survival varied by stage and molecular subtype. The 5-year OS rates for patients with stage I, Ⅱ, Ⅲ, and IV diseases were 96.5%, 91.6%, 74.8%, and 40.7%,respectively, and the corresponding estimates of 5-year CSS rates were 97.1%, 92.6%, 75.6%, and 42.7%, respectively.The 5-year OS rates for patients with luminal A, luminal B, HER2, and triple-negative subtypes of breast cancer were92.6%, 88.4%, 83.6%, and 82.9%, respectively, and the corresponding estimates of 5-year CSS rates were 93.2%, 89.1 %,85.4%, and 83.5%, respectively. Multivariate analysis showed that stage at diagnosis and molecular subtype were important prognostic factors for breast cancer.Conclusions: Survival of breast cancer patients varied significantly by stage and molecular subtype. Cancer screening is encouraged for the early detection and early diagnosis of breast cancer. More advanced therapies and health care policies are needed on HER2 and triple-negative subtypes.
文摘Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.
基金supported by the National key research and development project [2017YFC1200505]the National Science and Technology Major Project of China [2018ZX10711001,2018ZX10101-002]the Development Grant of State Key Laboratory of Infectious Disease Prevention and Control [2015SKLID505,2014SKLID103]
文摘Objective Tick-borne encephalitis virus(TBEV) is an emerging pathogen in Europe and North Asia that causes tick-borne encephalitis(TBE). A simple, rapid method for detecting TBEV RNA is needed to control this disease. Methods A reverse-transcription recombinase-aided amplification(RT-RAA) assay was developed. This assay can be completed in one closed tube at 39℃ within 30 minutes. The sensitivity and specificity of RT-RAA were validated using non-infectious synthetic RNA representing a fragment of the NS5 region of the wild-type(WT) TBEV genome and the Senzhang strain. Additionally, 10 batches of tick samples were used to evaluate the performance of the RT-RAA assay. Results The analytical limit of detection of the assay was 20 copies per reaction of the TBEV synthetic transcript and 3 plaque-forming units(pfu) per reaction of TBEV titers. With the specific assay, no signal due to other arboviruses was observed. Of the 10 batches of tick samples obtained from the Changbai Mountains of China, three were TBEV-positive, which was consistent with the results of the quantitative real-time PCR assay. Conclusion A rapid, highly sensitive, specific, and easy-to-use method was developed for the detection of the TBEV Far-Eastern subtype.
基金Supported by FONACIT Project,No.G2005000408PEII Project,No.2012001201
文摘AIM To detect human papilloma virus(HPV) presence and to characterize cellular immune response in breast cancer patients. METHODS A total of 74 women were included, of which 48 samples were from patients diagnosed with breast cancer and 26 patients with benign pathology of the breast. Molecular subtype classification was performed based on the immunohistochemical reports of the tumor piece. HPV genome detection and genotyping from fresh breast biopsies was performed using the INNO-LIPA HPV Genotyping Extra test(Innogenetics, Ghent, Belgium). CD3+, CD4+, CD8+ and natural killer(NK)+ cells levels from peripheral blood samples from patients with breast cancer and benign pathology were measured by flow cytometry. RESULTS Luminal A was the most frequent breast cancer molecular subtype(33.33%). HPV was detected in 25% of the breast cancer patients, and genotype 18 was the most frequent in the studied population. The mean of CD3+, CD4+ and CD8+ subpopulations were decreased in patients with breast cancer, in relation to those with benign pathology, with a statistically significant difference in CD8+ values(P = 0.048). The mean of NK+ cells was increased in the benign pathology group. The average level of CD3+, CD4+, CD8+ and NK+ cells decreased as the disease progressed. HER2+ and Luminal B HER2+ tumors had the lowest counts of cell subsets. HPV breast cancer patients had elevated counts of cellular subsets. CONCLUSION Determining level changes in cellular subsets in breast cancer patients is a useful tool to evaluate treatment response.
基金the National Key R&D Program of China(2017YFA0104900)the National Natural Science Foundation of China(81630065,31830029,and 81802195)the China Postdoctoral Science Foundation(2017M621913).
文摘The limited molecular classifications and disease signatures of osteoarthritis(OA)impede the development of prediagnosis and targeted therapeutics for OA patients.To classify and understand the subtypes of OA,we collected three types of tissue including cartilage,subchondral bone,and synovium from multiple clinical centers and constructed an extensive transcriptome atlas of OA patients.By applying unsupervised clustering analysis to the cartilage transcriptome,OA patients were classified into four subtypes with distinct molecular signatures:a glycosaminoglycan metabolic disorder subtype(C1),a collagen metabolic disorder subtype(C2),an activated sensory neuron subtype(C3),and an inflammation subtype(C4).Through ligand-receptor crosstalk analysis of the three knee tissue types,we linked molecular functions with the clinical symptoms of different OA subtypes.For example,the Gene Ontology functional term of vasculature development was enriched in the subchondral bone-cartilage crosstalk of C2 and the cartilage-subchondral bone crosstalk of C4,which might lead to severe osteophytes in C2 patients and apparent joint space narrowing in C4 patients.Based on the marker genes of the four OA subtypes identified in this study,we modeled OA subtypes with two independent published RNA-seq datasets through random forest classification.The findings of this work contradicted traditional OA diagnosis by medical imaging and revealed distinct molecular subtypes in knee OA patients,which may allow for precise diagnosis and treatment of OA.
基金the National Key Research and Development Program of China(2016YFD0500201)the Shandong “Double Tops” Program,China
文摘To investigate the epizootic of swine influenza virus(SIV),60 nasal swabs were collected from a clinical cases of pig farm in Tai’an City,Shandong Province of China in April 2017.SIV was isolated by inoculating into 10-day-old Special Pathogen Free embryonated eggs and the whole genome was sequenced.An H1N1 subtype SIV was isolated and designated as A/swine/Shandong/TA04/2017(H1N1).Phylogenetic analysis showed that apart from the polymerase A(PA) fragment belonging to the 2009 pandemic H1N1 branch,seven genome segments belonged to avian-like H1N1 influenza virus lineage.The cleavage site sequence of the hemagglutinin(HA) protein was PSIQSR↓G,which is a typical molecular biological characteristic.Five potential N-glycosylation sites(N14,N26,N277,N484 and N543) were found in the HA gene.To further investigate the epidemiology of SIV in this farm,the 995 serum samples were assessed with EAH1N1 2009 pandemic H1N1 and H3 N2 antigens.The results showed that the total positive rate was 65.43%.The positive rates of single virus infection detected by EAH1N1,2009 pdmH1N1 and H3 N2 for serum HI(Hemagglutination inhibition) were 48.35,30.85 and 7.47%,respectively.The results showed that SIV in Shandong Province has been reassorted in some segments and the SIV-positive rate was high on the SIV outbreak farm.These data provide evidence of an epizootic of SIV.
文摘Intrahepatic cholangiocarcinoma is macroscopically classified into three subtypes, mass-forming-type, periductal infiltrating-type, and intraductal growth-type. Each subtype should be preoperatively differentiated to perform the valid surgical resection. Recent researches have revealed the clinical, radiologic, pathobiological characteristics of each subtype. We reviewed recently published studies covering various aspects of intrahepatic cholangiocarcinoma(ICC), focusing especially on the macroscopic subtypes and stem cell features to better understand the pathophysiology of ICC and to establish the valid therapeutic strategy.
文摘BACKGROUND Carcinoma of the ampulla of Vater is an uncommon ampullo-pancreatobiliary neoplasm,and the most common histological type is adenocarcinoma with a tubular growth pattern.Invasive micropapillary carcinoma(IMPC)is an aggressive variant of adenocarcinoma in several organs that is associated with lymph node metastasis and poor prognosis.IMPC was first described as a histological subtype of breast cancer;however,IMPC of the ampulla of Vater is extremely rare,with only three articles reported in the English literature.CASE SUMMARY We have reported a case of IMPC of the ampulla of Vater in an 80-year-old man.Microscopically,the surface area of the carcinoma was composed of tubulopapillary structures mimicking intra-ampullary papillary-tubular neoplasm,and the deep invasive front area exhibited a pattern of IMPC.The carcinoma showed lymphatic invasion and extensive lymph node metastasis.The immunohistochemical study revealed mixed intestinal and gastric/pancreatobiliary phenotypes.CONCLUSION This rare subtype tumor in the ampulla of Vater showed a histologically mixed phenotype and exhibited aggressive behavior.
文摘Our knowledge of renal cell carcinoma(RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC.
文摘The brain tumor perivascular niche(PVN),the region in the vicinity of microvessels is a prime location for brain tumor stem-like cells(BTSCs)[1].Tumor microvasculature creates a complex microenvironment consisting of various cell types,the extracellular matrix,and soluble factors that mediate cell-cell interaction.The brain tumor PVN controls maintenance,expansion,and differentiation of BTSCs via direct cell contact or paracrine signaling cues.BTSCs often receive bidirectional crosstalk from endothelial cells and other cell types in the niche[2].In addition,the perivascular zone may serve as a path for tumor cells to migrate over long distances(3,4)Unlike other solid tumors,glioblastoma multiforme(GBM)cells rarely metastasize to other organs,but they can invade the entire brain by migrating along specific brain tissue structures,such as blood vessels or white matter tracts,leading to high rates of relapse.Despite the success in modeling diffuse brain tumors in both genetically-modified and patient-derived xenograft(PDX)animals,there is an unmet need for an in vitro system that can bridge conventional cell culture and animal models by mimicking not only the anatomy but also the function of the PVN to study the dynamics of BTSCs.In this presentation,I will describe the use of a microvasculature-on-a-chip system as a PVN model to evaluate the dynamics of BTSCs ex vivo from 10 glioblastoma patients [5].We observed that BTSCs preferentially localize in the perivascular zone.Live cell tracking showed that the cells residing in the vicinity of microvessels had the lowest motility,while a fraction of cells on the microvessels unexpectedly possessed the highest motility and migrated over the longest distance.These results indicate that the perivascular zone is a niche for BTSCs,while the microvascular tracks are also a path for long-distance tumor cell migration and invasion.Additionally,the degree of co-localization between tumor cells and microvessels varied significantly across patients.To validate the results from our microvasculature-on-a-chip system,we used single-cell transcriptome sequencing(10 patients and 21,750 single cells in total)to identify the subtype of each tumor cell.The co-localization coefficient was found to correlate positively with proneural(stem-like)or mesenchymal(invasive)but not classical(proliferative)tumor cells.Furthermore,we found that a gene signature profile including PDGFRA correlated strongly with the'homing'of brain tumor cells to the PVN.Our findings demonstrated that ex vivo dynamics of human brain tumor cells in a microvasculature-on-a-chip model can recapitulate in vivo tumor cell dynamics,heterogeneity,and subtypes,representing a new route to the study of human tumor cell biology and uncover patient-specific tumor cell functions.Acknowledgments:We thank Drs.Laura Niklason,Eric Holland,Franziska Michor,and Frank Szulzewsky for scientific discussion.We thank Misha Guy,Vladimir Polejaev,Zhenting Jiang,and Alice Yun for suggestions and help on the simulation computing and SEM/confocal imaging process.This research was supported by the Packard Fellowship for Science and Engineering(R.F.),National Science Foundation CAREER Award CBET-1351443(R.F.),U54 CA193461(R.F.),U54CA209992(Sub-Project ID:7297 to R.F.),R01 NS095817(J.Z.),Yale Cancer Center Co-Pilot Grant(to R.F.).The molds for microfluidic devices were fabricated in the Yale School of Engineering and Applied Science cleanroom.Sequencing was performed at the Yale Center for Genome Analysis(YCGA)facility.Data was analyzed at Yale High Performance Computing(HPC)center.Super resolution confocal imaging was performed at Yale Center for Cellular and Molecular Imaging(CCMI).
基金supported by the National Natural Science Foundation of China(Grant No.81502309)。
文摘Objective:The aim of the study was to identify specific chemosensitivity drugs for various molecular subtypes of breast tumors in Chinese women,by detecting the expression of drug resistance genes and by using the drug sensitivity test on different molecular subtypes of breast cancers.Methods:The expression of drug resistance genes including Topo Ⅱ,GST-π,P-gp,LRP,and CD133 were detected with immunohistochemistry in a tissue microarray.Drug sensitivity tests included those for paclitaxel,epirubicin,carboplatin,vinorelbine,and fluorouracil and were conducted on primary cancer tissue cells and cell lines,including the T47 D,BT-474,and MDA-MB-231 cells and human breast cancer xenografts in nude mice.Results:The different drug resistant genes Topo Ⅱ,GST-π,P-gp,and LRP were differentially expressed among different molecular subtypes of breast cancers(P<0.05).Positive expression of CD133 was highest in basal-like breast cancer(P<0.05).Kaplan-Meier survival analysis showed that positive expressions of Topo Ⅱ and CD133 both correlated with shorter disease-free survival(DFS)(P<0.05)and overall survival(P<0.05),and positive expression of LRP correlated only with shorter DFS(P<0.05).BT-474 showed chemosensitivity to paclitaxel and epirubicin,while MDA-MB-231 showed chemosensitivities to paclitaxel,epirubicin,carboplatin,and fluorouracil(T/C≤50%).The basal-like and HER2+breast cancer primary cells showed chemosensitivities to paclitaxel and epirubicin with significant differences compared with luminal breast cancer primary cells(P<0.05).Conclusions:The differential expression of drug resistance genes and the differential chemosensitivities of drugs in different molecular subtype of breast cancers suggested that individual treatment should be given for each type of breast cancer.
基金financially supported with General Project of Nat-ural Science Foundation of China (No. 21373252)
文摘Research the evaporating crystalization process of the magnesium sulfate subtypes brine at high temperature from Dalangtan salt lake in Qinghai province.It was revealed that the salt lake is a typical subtype
基金supported by the National Key R&D Program of China(2016YFD0500800)。
文摘H7 avian influenza viruses(AIVs) normally circulated among birds before. From 1996 to 2012, human infections with H7 AIVs(H7 N2, H7 N3, and H7 N7) were reported in Canada, Italy, Mexico, the Netherlands, the United Kingdom and the USA. Until March 2013, human infections with H7 N9 AIVs were reported in China. Since then, H7 N9 AIVs have continued to circulate in both humans and birds. Therefore, the detection of antibodies against the H7 subtype of AIVs has become an important topic. In this study, a competitive enzyme-linked immunosorbent assay(cELISA)method for the detection of antibody against H7 AIVs was established. The optimal concentration of antigen coating was 5 μg mL^(-1), serum dilution was 1/10, and enzyme-labeled antibody was 1/3 000. To determine the cut-off value of cELISA, percent inhibition(PI) was determined by using receiver operating characteristic(ROC) curve analysis in 178 AIVs negative samples and 368 AIVs positive serum samples(n=546). When PI was set at 40%, the specificity and sensitivity of cELISA were 99.4 and 98.9%, respectively. This method could detect the antibodies against H7 Nx(N1–N4, N7–N9) AIVs, and showed no reaction with AIVs of H1–H6 and H8–H15 subtypes or common avian viruses such as Newcastle disease virus(NDV), Infectious bronchitis virus(IBV) and Infectious bursal disease virus(IBDV), exhibiting good specificity. This method showed a coincidence rate of 98.56% with hemagglutinin inhibition(HI) test. And the repeatability experiment revealed that the coefficients of variation(CV) of intra-and inter-batch repetition were all less than 12%. The data indicated that the cELISA antibody-detection method established in this study provided a simple and accurate technical support for the detection of a large number of antibody samples of H7-AIV.
