Blood typing and transfusion therapy in a patient with A2 subtype acute myeloid leukemia M2:A case report

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.

Detection of short stature homeobox 2 and RAS-associated domain family 1 subtype A DNA methylation in interventional pulmonology

One of the most important aspects of interventional pulmonology is to obtain tissue or liquid samples of the chest to diagnose a respiratory disease;however,it is still possible to obtain insufficient tissue or cytologic specimens.Indeed,methylation detection is an effective method by which to establish a diagnosis.This review focuses on the clinical application of short stature homeobox 2 and RAS-associated domain family 1 subtype A DNA methylation detection in interventional pulmonology,including bronchoscopic fluid biopsy,transbronchial needle aspiration,and pleural effusion.

Multiple RT-PCR Detection of H5,H7,and H9 Subtype Avian Influenza Viruses and Newcastle Disease Virus

Objective:This paper focuses on the multiple detection RT-PCR technology of H5,H7,AND H9 subtype avian influenza viruses and Newcastle disease virus,and points out the specific detection methods and detection procedures of avian influenza and Newcastle disease virus.Methods:The genes of Newcastle disease virus carrying out the HA gene sequence of H5,H7 and H9 subtype AIV in GenBank were used to establish a strategy for simultaneous detection of three subtypes of avian influenza virus and Newcastle disease virus.Results:The results showed that the program can detect and distinguish H5,H7 and H9 subtype avian influenza viruses and Newcastle disease virus at one time.Conclusion:Multiple RT-PCR detection method has high detection sensitivity and can detect and determine different subtypes of avian influenza virus and Newcastle disease virus quickly and accurately,therefore,it has a crucial role in the detection and control of avian influenza H5,H7 and H9 subtypes and Newcastle disease.

Genetic Variation Analysis on the Whole Genomic Sequence of a H9N2 Subtype Avian Influenza Virus Isolate

A Objective3 This study was to understand the genetic variation characters of the H9N2 subtype avian influenza virus isolate （A/Chicken/ Hebei/WD/98, abbreviated as WD98） by comparing with other reference strains. I-Method3 Eight complete genes were amplified by RT-PCR and sequenced. The homology and genetic evolution relationship were analyzed between these sequences and that of the seven reference strains. [Result] The whole genomic sequence of WD98 strain was 91.1% -95.8% homologous to that of seven reference strains tested. This isolate shared the highest homology （95.8%） to D/HK/Y280/97 and the lowest homology （91.1% ） to C/Pak/2/99. The HA cleavage site of the WD98 strain was R-S-S-R G, and the 226th amino acid at receptor-binding site was Gin. [ Condmion] WD98 strain belongs to mildly pathogenic avian in- fluenza virus and may not infect human. The genetic relationship is the closest between A/Chicken/Hebei/wD/98 and A/duck/HongKong/Y280/ 97, both of which belong to the sub-line of A/Chicken/Beijing/1/94 in Eurasian line. And A/Chicken/Hebei/WD/98 and A/Chicken/Beijing/1/94 are genetically distant within the same sub-line.

Long-term Follow-up Study on Gastric Intestinal Metaplasia Subtype and Its Relation to Expression of P53,Bcl-2 and PCNA

Objective： To investigate the correlation of typies of gastric intestinal metaplasia（IM）, expression of p53, bcl-2 and the proliferating cell nuclear antigen（PCNA）, with the lesion＇s evolution. Methods： A total of 80 patients with IM（53 male and 27 female, 35-64 years old） from an area with high-risk of gastric cancer（GC） in China were enrolled into this prospective study, including 28 cases of type Ⅰ （complete）, 25 cases of type Ⅱ （incomplete） , and 27 cases of type Ⅲ （incomplete）. Of the 80 cases, 62 cases including 19 cases of type Ⅰ, 22 type Ⅱ and 21 type Ⅲ, were followed up for 5-14 years（49 cases for 14 years, 6 for 10 years, and 7 for 5 years）. All of the 80 cases were studied immunohistochemically for the expression of p53, bcl-2 and PCNA. Results： The rate of p53-expressing cases was higher in type Ⅲ（25.9%） than in type Ⅰ（10.7%） and type Ⅱ （12.0%）, but without statistical significance（P=0.3070）. The positive rate of bcl-2 was obviously lower in type Ⅰ （21.4%） and type Ⅱ （24.0%） than in type Ⅲ（37.0%）, but not statistically significant（P=0.4223）. We observed difference in PCNA labelling index （LI） between type Ⅱ and type Ⅲ（P=0.0037）, and the difference was particularly significant in type Ⅰ as compared with type Ⅲ（P〈0.0001）. There was no statistical significance between type I and type II （P=0.0616）. Evolution into GC was detected in 0%, 4.5%, and 14.3% of type Ⅰ, type Ⅱ, and type Ⅲ IM cases, respectively. Progression to dysplasia was detected in 31.6%, 18.2%, and 14.3% of type Ⅰ, type Ⅱ, and type Ⅲ IM cases, respectively. Persistence of IM was documented in 31.6%, 45.5%, and 42.9% of type Ⅰ, type Ⅱ, and type Ⅲ IM cases, respectively. Regression of IM was documented in 36.8%, 31.8%, and 28.6% of type Ⅰ, type Ⅱ, and type ⅢIM cases, respectively. In progressive, persistent and regressive groups, the positive rates of p53 were 17.6%, 16.0% and 15.0%, bcl-2 were 29.4%, 36.0% and 25.0%, and PCNA LIs were 24.953±14.477, 23.752±12.934 and 25.105±10.055, respectively. There were no significant differences between the groups. Conclusion： The present follow-up study indicated that type Ⅲ had a higher risk for development of cancer than type Ⅰ or Ⅱ. PCNA LI was significantly higher in type Ⅲthan in type Ⅰ and Ⅱ, suggesting that cell proliferation in type Ⅲwas more active. Our data also indicated that the expression of p53 and bcl-2 had no apparent association with the particular type and the expression of p53, bcl-2 and PCNA had no apparent correlation with evolution of IM. Further studies with a larger sample size are needed to verify present observation.

A duplex RT-PCR assay for detection of H9 subtype avian influenza viruses and infectious bronchitis viruses

H9 s ubtype avian influenza virus（AIV） and infectious bronchitis virus（IBV） are major pathogens circulating in poultry and have resulted in great economic losses due to respiratory disease and reduced egg production. As similar symptoms are elicited by the two pathogens, it is difficult for their differential diagnosis. So far, no reverse transcription-polymerase chain reaction（RT-PCR） assay has been found to differentiate between H9 AIV and IBV in one reaction. Therefore, developing a sensitive and specific method is of importance to simultaneously detect and differentiate H9 AIV and IBV. In this study, a duplex RT-PCR（d RT-PCR） was established. Two primer sets target the hemagglutinin（HA） gene of H9 AIV and the nucleocapsid（N） gene of IBV, respectively. Spec ific PCR products were obtained from all tested H9 AIVs and IBVs belonging to the major clades circulating in China, but not from AIVs of other subtypes or other infectious avian viruses. The sensitivity of the d RT-PCR assay corresponding to H9 AIV, IBV and mixture of H9 AIV and IBV were at a concentration of 1×10^1, 1.5×10^1 and 1.5×10^1 50% egg infective doses（EID_（50）） m L^–1, respectively. The concordance rates between the d RT-PCR and virus isolation were 99.1 and 98.2%, respectively, for detection of samples from H9N2 AIV or IBV infected chickens, while the concordance rate was 99.1% for detection of samples from H9N2 AIV and IBV co-infected chickens. Thus, the d RT-PCR assay reported herein is specific and sensitive, and suitable for the differential diagnosis of clinical infections and survei llance of H9 AIVs and IBVs.

Identification of prognostic molecular subtypes and model based on CD8+ T cells for lung adenocarcinoma

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.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province,China,2014–2020

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.

Identification of tumor antigens and immune subtypes of hepatocellular carcinoma for mRNA vaccine development

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.

Rare synchronous colorectal carcinoma with three pathological subtypes: A case report and review of the literature

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.

Classification of patients with metastatic colorectal cancer into consensus molecular subtypes into real-world: A pilot study

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.

The influence of stage at diagnosis and molecular subtype on breast cancer patient survival: a hospital.based multi.center study

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.

Risk Factors, Clinical Features and Prognosis for Subtypes of Ischemic Stroke in a Chinese Population

It is unanimously accepted that stroke is a highly heterogeneous disorder. Different subtypes of ischemic stroke may have different risk factors, clinical features, and prognoses. The aim of this study was to evaluate the risk factors, clinical characteristics, and prognoses of different subtypes of ischemic stroke defined by the Trial of ORG10172 in Acute Stroke Treatment （TOAST） criteria. We prospectively analyzed the data from 530 consecutive patients who were admitted to our hospital with acute ischemic stroke within 7 days of stroke onset during the study period. Standardized data assessment was used and the cause of ischemic stroke was classified according to the TOAST criteria. Patients were followed up till 30 and 90 days after stroke onset. It was found that large-artery atherosclerosis was the most frequent etiology of stroke （37.4%）, and showed the highest male preponderance, the highest prevalence of previous transient ischemic attack, and the longest hospital stay among all subtypes. Small artery disease （36.4%） was associated with higher body mass index, higher plasma triglycerides, and lower plasma high-density lipoprotein cholesterol than cardioembolism. Cardioembolism （7.7%）, which was particularly common in the elderly （i.e., individuals aged 65 years and older）, showed the highest female preponderance, the highest prevalence of atrial fibrillation, the earliest presentation to hospital after stroke onset, the most severe symptoms on admission, the maximum complications associated with an adverse outcome, and the highest rate of stroke recurrence and mortality. Our results suggest that ischemic stroke should be regarded as a highly heterogeneous disorder. Studies involving risk factors, clinical features, and prognoses of ischemic stroke should differentiate between etiologic stroke subtypes.

Genomic alterations and molecular subtypes of gastric cancers in Asians

Gastric cancer(GC) is a highly heterogenic disease,and it is the second leading cause of cancer death in the world.Common chemotherapies are not very effective for GC,which often presents as an advanced or metastatic disease at diagnosis.Treatment options are limited,and the prognosis for advanced GCs is poor.The landscape of genomic alterations in GCs has recently been characterized by several international cancer genome programs,including studies that focused exclusively on GCs in Asians.These studies identified major recurrent driver mutations and provided new insights into the mutational heterogeneity and genetic profiles of GCs.An analysis of gene expression data by the Asian Cancer Research Group(ACRG) further uncovered four distinct molecular subtypes with well-defined clinical features and their intersections with actionable genetic alterations to which targeted therapeutic agents are either already available or under clinical development.In this article,we review the ACRG GC project.We also discuss the implications of the genetic and molecular findings from various GC genomic studies with respect to developing more precise diagnoses and treatment approaches for GCs.

A Reverse-transcription Recombinase-aided Amplification Assay for the Rapid Detection of the Far-Eastern Subtype of Tick-borne Encephalitis Virus

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.

Biological subtypes of breast cancer: Prognostic and therapeutic implications

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.

Breast Cancer Subtypes and Survival in Chinese Women with Operable Primary Breast Cancer

Objective： To investigate the associations between the different breast cancer subtypes and survival in Chinese women with operable primary breast cancer. Methods： A total of 1538 Chinese women with operable primary breast cancer were analyzed in this study, the median follow-up was 77 months. Estrogen receptor （ER）, progesterone receptor （PR）, and HER2 status were available for these patients. Results： Luminal A （ER＋ and/or PR＋, HER2-） had a favorable disease-free survival （DFS） and overall survival （OS） compared with other subtypes in the entire cohort. Using the luminal A as a reference, among the patients with lymph node positive disease, HER2＋ （ER-, PR-, HER2＋） had the worst DFS （hazard ratio, HR=1.80, 95% CI 1.11 to 2.91, P=0.017） and luminal B （ER＋ and/or PR＋, HER2＋） had the worst OS （HR=2.27, 95% CI 1.50 to 3.45, P0.001）; among the patients with lymph node negative disease, triple-negative （ER-, PR-, HER2-） had the worst DFS （HR=2.21, 95% CI 1.43 to 3.41, P0.001）, whereas no significant difference in DFS between HER2＋ and luminal B or luminal A was observed. Conclusion： As compared with luminal A, luminal B and HER2＋ have the worst survival in patients with lymph node positive disease, but this is not the case in patients with lymph node negative disease; triple-negative subtype has a worse survival in both lymph node positive and lymph node negative patients.

Comparative Analysis of General Characteristics of Ischemic Stroke of BAD and non-BAD CISS Subtypes

Summary： Based on the recently proposed Chinese ischemic stroke subclassification （CISS） system, intracranial branch atheromatous disease （BAD） is divided into large artery atherosclerosis （LAA） and penetrating artery disease （PAD）. In the current retrospective analysis, we compared the general charac- teristics of BAD-LAA with BAD-PAD, BAD-LAA with non-BAD-LAA and BAD-PAD with non-BAD-PAD. The study included a total of 80 cases, including 45 cases of BAD and 35 cases of non-BAD. Subjects were classified using CISS system： BAD-LAA, BAD-PAD, non-BAD-LAA and non-BAD-PAD. In addition to analysis of general characteristics, the correlation between the factors and the two subtypes of BAD was evaluated. The number of cases included in the analysis was： 32 cases of BAD-LAA, 13 cases of BAD-PAD, 21 cases of non-BAD-LAA, and 14 cases of non-BAD-PAD. Dia- betes mellitus affected more non-BAD-LAA patients than BAD-LAA patients （P=0.035）. In comparison with non-BAD-PAD, patients with BAD-PAD were younger （P=-0.040）, had higher initial NIHSS score （P〈0.001） and morbidity of ischemic heart disease （P=0.033）. Within patients with BAD, the PAD sub- type was associated with smoking （OR=0.043; P=0.011）, higher low-density lipoprotein （OR=5.339; P=0.029）, ischemic heart disease （OR=9.383; P=0.047） and diabetes mellitus （OR=12.59;P=-0.020）. It was concluded that large artery atherosclerosis was the primary mechanism of BAD. The general char- acteristics showed no significant differences between the CISS subtypes of LAA and PAD within BAD, as well as between the BAD and non-BAD within LAA subtype. Several differences between PAD sub- types of BAD and non-BAD were revealed.

Clinicopathological Features of Breast Cancer with Different Molecular Subtypes in Chinese Women

A retrospective study was performed to explore the relationship between molecular subtypes and clinicopathological features of breast cancer in Chinese women. Six hundred and twenty-eight Chi- nese women with breast cancer were classified into four molecular subtypes according to their estrogen receptor （ER）, progesterone receptor （PR） and Her-2 status. The prevalence rate of each molecular sub- type was analyzed. Relationship between the subtypes and clinicopathologic features was determined. The distribution of molecular subtypes was as follows： luminal A 46.5%, luminal B 17.0%, basal 21.5%, HER2/neu 15.0%. The subtypes had no significant difference under different menopausal status. How- ever, in the age-specific groups, the age group of〈35 years was more likely to get basal cell-like cancer （36.9%）. Statistically significant differences were found among molecular subtypes by age, nuclear grade, tumor size, lymph node （LN） metastasis, tumor stage by American Joint Committee on Cancer （AJCC）, radiotherapy but not by chemotherapy, types of surgery. After adjusting for several relative confounding factors, the basal subtype more likely had lower nodal involvement in both the incidence of LN metastasis （〉1 positive LN） and incidence of high-volume LN metastasis （〉4 positive LN）. The HER2/neu subtype had higher nodal involvement in the incidence of high-volume LN metastases. After adjusting for relative confounding factors, the HER2/neu subtype more likely had higher AJCC tumor stages. It was suggested that there existed close relationship between molecular subtypes and clinicopa- thological features of breast cancer. In addition, the breast cancer subtypes have been proven to be an independent predictor of LN involvement and AJCC tumor stage. These findings are very important for understanding the occurrence, development, prognosis and treatment of breast cancer in Chinese popu-lation.

Subtype Identification of Avian Influenza Virus on DNA Microarray

We have developed a rapid microarray-based assay for the reliable detection of H5, H7 and H9 subtypes of avian influenza virus （AIV）. The strains used in the experiment were A/Goose/Guangdong/1/96 （H5N1）, A/African starling/983/79 （H7N1） and A/Turkey/Wiscosin/1/66 （H9N2）. The capture DNAs clones which encoding approximate 500-bp avian influenza virus gene fragments obtained by RT-PCR, were spotted on a slide-bound microarray. Cy5-labeled fluorescent cDNAs, which generated from virus RNA during reverse transcription were hybridized to these capture DNAs. These capture DNAs contained multiple fragments of the hemagglutinin and matrix protein genes of AIV respectively, for subtyping and typing AIV. The arrays were scanned to determine the probe binding sites. The hybridization pattern agreed approximately with the known grid location of each target. The results show that DNA microarray technology provides a useful diagnostic method for AIV.