临床和实验室科学年鉴欢迎报告临床科学研究的手稿，包括病理学、临​​床化学、生物技术、分子生物学、细胞遗传学、微生物学、免疫学、血液学、输血医学、器官和组织移植、治疗学、毒理学和临床信息学。

The Annals of Clinical and Laboratory Science welcomes manuscripts reporting on clinical science research, including areas such as pathology, clinical chemistry, biotechnology, molecular biology, cytogenetics, microbiology, immunology, hematology, transfusion medicine, organ and tissue transplantation, therapeutics, toxicology, and clinical informatics.

《Annals of Clinical and Laboratory Science》欢迎提交关于临床科学研究的手稿，涵盖的领域包括病理学、临床化学、生物技术、分子生物学、细胞遗传学、微生物学、免疫学、血液学、输血医学、器官和组织移植、治疗学、毒理学以及临床信息学。

Annals of Clinical and Laboratory Science

Alzheimer's disease (AD) is a neurodegenerative disease caused by both genetic and environmental factors. This study aimed to explore the underlying molecular mechanism of AD by bioinformatic gene analysis. The gene expression profiles of GSE16759 and GSE28146 were downloaded, and co-differentially expressed genes (co-DEGs) were identified by R software. Subsequently, the data were analyzed using a combined bioinformatics approach and predicted the microRNAs (miRNAs) targeting the key gene using miRNA databases. Based on the results of these analyses, ADAMTS1, CITED2, and GABRA2 were identified as co-DEGs. They were all associated with learning disorders (inference Score: 103.22, 140.41, and 96.26, respectively) and memory disorders (inference Score: 102.77, 132.68, and 81.80, respectively). The hub-genes of ADAMTS1, CITED2, and GABRA2 may be associated with AD. Additionally, miR-548c- 3p is probably a common target for ADAMTS1, CITED2, and GABRA2.

Xiaoye Ma

Guilin Meng

Minjie Zhang

Yichen Zhao

Yuchen Zhou

Yanxin Zhao

Xueyuan Liu

Annals of clinical and laboratory science

Exploring Potential Biomarkers Underlying the Pathogenesis of Alzheimer's Disease by Bioinformatics Gene Analysis.

通过生物信息学基因分析探索阿尔茨海默病发病机制中的潜在生物标志物。

Here we present the case of a 73-year-old male with rectal adenocarcinoma with heterotopic ossification (HO). Cancer-associated HO in the digestive system is rare. Thus, the precise mechanism and clinicopathological significance of HO have not yet been defined. To clarify the molecular mechanisms of HO, we analyzed the expression levels of signaling molecules related to epithelial-mesenchymal transition (EMT) that lead to ossification in the tumor cells discriminating the ossified area (HO-area) and non-ossified area (non-HO area). Expression levels of BMP4 were elevated in both areas, whereas BMP2 was specifically increased in the HO-area by qPCR. EMT-related molecules such as Snail and Slug were especially higher in the HO-area. By immunohistochemistry, the expression of Smad4, nuclear staining of β-catenin, and the phosphorylated form of GSK-3β were detectable in both areas, and GSK-3β was highly phosphorylated in the HO-area. The tumor growth rate was extremely high, with the Ki-67 labeling index at 90%. In the HO-area, osteoblasts with alkaline phosphatase expression were distributed surrounding the tumor cells. This is the first demonstration of the involvement of EMT in HO of colon cancer through BMP/SMAD and WNT/β-catenin signaling pathways, which are especially prominent in the HO-area leading to the osteogenic property.

Naho Katono

Masumi Tsuda

Jun Suzuka

Yoshitaka Oda

Lei Wang

Zen-Ichi Tanei

Mishie Tanino

Takanobu Ohata

Eisuke Nagabuchi

Yusuke Ishida

Shunsuke Kimura

Toshihiko Iwanaga

Shinya Tanaka

Involvement of BMP and Wnt Signals Leadingto Epithelial-Mesenchymal Transition in Colon Adenocarcinoma with Heterotopic Ossification.

BMP和Wnt信号在异位骨化结肠腺癌中导致上皮-间质转化的作用。

Objective To investigate the role and potential underlying mechanism of miR-93-5p in the carcinogenesis and gemcitabine resistance of pancreatic cancer (PC) cells. Methods We generated a gemcitabine-resistant PC cell line Bxpc-3/GemR following prolonged gemcitabine exposure to its parental gemcitabine-sensitive counterpart Bxpc-3/Par. Cell viability was monitored by MTS assay. Transfection was performed using Lipofectamine 3000 reagent. Cell apoptosis and rhodamine 123 fluorescence were detected by flow cytometry. Luciferase activities were measured using the luciferase reporter gene assay. Expression analysis was carried out by qRT-PCR and western blot. Results Significantly increased viability and enhanced expression of the multi-drug resistance-1 (MDR1) gene were observed in Bxpc-3/GemR cells, in which miR-93-5p is considerably upregulated, compared with Bxpc-3/Par cells. Downregulation of miR-93-5p inhibited cell viability, induced cell apoptosis, and decreased MDR1 expression in Bxpc-3/GemR cells, whereas upregulation essentially reversed these properties in Bxpc-3/Par cells. We further confirmed that PTEN was a direct target of miR-93-5p, and overexpression of miR-93-5p was accompanied by a significant increase in the phosphorylation of Akt expression in the Bxpc-3/Par cells. Moreover, inhibition of PI3K/Akt signaling diminished MDR1 expression. Conclusion These observations suggest that miR-93-5p modulates tumorigenesis and gemcitabine resistance in PC cells via targeting the PTEN/PI3K/Akt signaling pathway.

Yinfang Wu

Weixing Xu

Yueming Yang

Zhongwei Zhang

miRNA-93-5p Promotes Gemcitabine Resistance in Pancreatic Cancer Cells by Targeting the PTEN-Mediated PI3K/Akt Signaling Pathway.

miRNA-93-5p通过靶向PTEN介导的PI3K/Akt信号通路促进胰腺癌细胞对吉西他滨的耐药性。

Mutations of phosphatidylinositol glycan biosynthesis class T (PIGT), which encodes a subunit of the glycosylphosphatidylinositol (GPI) transamidase complex, can lead to multiple anomalies, including seizures, intellectual disabilities, facial dysmorphism, and various congenital malformations. We performed whole-exome sequencing in a patient with seizures, intellectual disabilities, truncal ataxia, facial dysmorphism, and persistent hypophosphatasia without rickets or bone mineralization defects, and identified two heterozygous mutations in PIGT, c.250G>T (p.Glu84*) and c.1582G>A (p.Val528Met). GPI-linked protein analyses found no abnormalities. Although the patient's hypophosphatasia persists, no skeletal, urological, or dental abnormalities were found. The seizures disappeared after administering antiepileptic drugs. PIGT mutations should be considered in patients with multiple congenital symptoms and persistent hypophosphatasia.

Yun Jung Hur

Bo Lyun Lee

Woo Yeong Chung

Shinae Yu

Kyung Ran Jun

Seung Hwan Oh

Compound Heterozygous PIGT Mutations in Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome: First Case in Korea and Characterization by Persistent Hypophosphatasia.

韩国首例多发性先天异常-肌张力低下-癫痫综合征中的复合杂合PIGT突变及持续性低磷酸酯酶症的特征分析。

OBJECTIVE Procalcitonin levels above 2.0 ng/mL are associated with a higher risk of severe sepsis. Bacteremia with procalcitonin levels lower than 2.0 ng/mL has not received much attention, and relevant prediction models are lacking. Herein, a panel of biomarkers was used to establish an early predictive model for bacteremia using machine learning approaches. METHODS Retrospective evaluation of 487 non-bacteremia controls and 444 bacteremia patients with low-level procalcitonin was performed. Clinical data, including procalcitonin, interleukin-6, C-reactive protein, D-dimer, and lactic acid levels, as well as leukocyte, neutrophil, and platelet counts, were used to identify a panel of relevant variables to build a machine learning model. RESULTS By comparing six prediction models, the performance of an artificial neural network (ANN) was found to be superior to that of other designed models, with a sensitivity of 0.82, a specificity of 0.85, and an accuracy rate of 83.5%. Furthermore, interleukin-6, procalcitonin, D-dimer, and lactic acid were found to be the most influential biomarkers with the potential to predict bacteremia. CONCLUSION The ANN model described herein holds outstanding predictive performance, with the potential to provide real-time, data-driven predictions of bacteremia.

Mingkuan Su

Hongbin Chen

Jie Qiu

Jiancheng Huang

Four Biomarkers-Based Artificial Neural Network Model for Accurate Early Prediction of Bacteremia with Low-level Procalcitonin.

基于四种生物标志物的人工神经网络模型用于低水平降钙素原的早期准确预测菌血症。

OBJECTIVE Breast cancer is recognized as the most common cause of malignancy and cancer death worldwide; however, mutations in the cancer-related BRCA genes are detected in only 2-3% of patients with breast cancer. Because next-generation sequencing technology allows concurrent sequencing of numerous target genes, diverse cancer-susceptibility genes are now being evaluated, although their significance in clinical practice remains unclear. METHODS In this study, we developed a sequencing panel containing the genes BRCA1, BRCA2, TP53, PIK3CA, ERBB2 (Her2), and PTEN, which are all associated with cancer risk in patients, and we enrolled 60 patients with breast cancer. RESULTS Germline mutations were found to be carried by nine patients (15%): 3 in BRCA1, 5 in BRCA2, and 1 in TP53. The patients harboring these mutations are considered to face a high risk of developing malignant tumors, and cancer screening is thus recommended for the patients. CONCLUSION This study demonstrates the feasibility of using Ion Torrent sequencing technology for reliably detecting gene mutations in clinical practice for guiding individualized drug therapy or combination therapies for breast cancer.

Peng-Fei Liu

Zhong-Ling Zhuo

Fei Xie

Hai-Peng Xian

Chang Liu

Shu Wang

Xiao-Tao Zhao

Multiple Mutation Detection for Risk Assessment in Patients with Breast Cancer by Using Next-Generation Sequencing.

使用下一代测序技术对乳腺癌患者进行多重突变检测以评估风险。

Objective Severe aplastic anemia (SAA) is a fatal bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a matched sibling donor is the first-line treatment for older SAA patients. However, the number of CD34+ cells collected from a matched donor is often lower than expected. To overcome the problem, this study was conducted to combine a matched sibling donor with an unrelated cord blood transplantation for the treatment of a patient with SAA. Case report A 45-year-old male patient with SAA was treated with a sibling-matched allo-HSCT. Due to the low amount of donor CD34+ cells, an unrelated umbilical cord blood stem cell transplantation (UCBT) with 9/10 HLA matching was subsequently carried out. Successful hematopoietic reconstitution was achieved by the dual transplantation. Unexpectedly, beginning in the fourth month after transplantation, the sibling donor chimerism was transformed to a stable and complete UCB source. Conclusion This study provides evidence that UCB-derived HSCs have a higher capacity for hematopoietic reconstitution, suggesting that UCB plus an HLA-matched sibling donor is a good alternative for older patients with SAA.

Zhong-Ling Wei

Lai-Quan Huang

Yi-Zhi Jiang

Jia-Wei Yan

Na-Na Wang

Dong-Ping Huang

Durable Cord Blood Cell Engraftment in a Patient with Severe Aplastic Anemia after a Matched Sibling Bone Marrow Transplantation and an Unrelated Cord Blood Transplantation.

同胞骨髓移植和无关脐血移植后一名重型再生障碍性贫血患者中持久脐血细胞植入。

Objective microRNAs may play essential roles in the development and drug resistance of non-small cell lung cancer (NSCLC). However, their functions and mechanisms are not fully understood. Our goal was to define the role of miR-145-5p in the gefitinib resistance of NSCLC. Materials and methods An A549 gefitinib-resistant cell line and xenograft nude mice were used in this study. The expression of miR-145-5p and its targets, NRAS and MEST, were detected and measured by qPCR, Western blot, RNA-FISH, or immunofluorescence analysis. Results miR-145-5p was downregulated in gefitinib-resistant A549 cells (A549/Gef R). Overexpression of miR-145-5p enhanced the sensitivity to gefitinib and inhibited cell proliferation and invasion in A549/Gef R. miR-145-5p was also significantly reduced in LUAD and LUSC clinical samples and closely associated with a favorable prognosis, according to the UALCAN and TCGA databases. Moreover, NRAS and MEST were found to be downstream target genes of miR-145-5p and to function as oncogenes in NSCLC samples, and gefitinib resistance could be improved following the interference of these two molecules. Conclusion miR-145-5p improves the sensitivity of acquired gefitinib-resistant cells to gefitinib via inhibiting NRAS and MEST expression. The miR 145-5p-NRAS/MEST axis in NSCLC provides insights for the development of a NRAS/MEST targeting therapeutic approach to overcome gefitinib resistance in NSCLC patients.

Chuigong Yu

Bingqing Li

Jinghao Wang

Ziyue Zhang

Shengjing Li

Shixiong Lei

Qinhao Wang

miR-145-5p Modulates Gefitinib Resistance by Targeting NRAS and MEST in Non-Small Cell Lung Cancer.

miR-145-5p 通过靶向 NRAS 和 MEST 调节非小细胞肺癌中的吉非替尼耐药性。

OBJECTIVE Studies have confirmed that real-time PCR detection of Aspergillus DNA in bronchoalveolar lavage fluid (BALF) is more valuable than blood samples in the diagnosis of invasive pulmonary aspergillosis (IPA). The latest guidelines recommend the use of serum samples for Aspergillus antibody testing for chronic pulmonary aspergillosis (CPA). However, research on CPA diagnosed by real-time PCR testing of BALF has been limited. In this study, we assessed the clinical value of BALF GM and PCR detection in diagnosing CPA. METHODS The diagnostic criteria of this study were based on the 2015 ESCMID/ERS guidelines for CPA. Seventy-nine patients with CPA and 74 non-CPA patients were enrolled. Aspergillus DNA in BALF was detected in the patients with CPA. RESULTS The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of BALF PCR in the CPA group were 87.18%, 89.80%, 87.18%, 89.80%, and 0.89 (95% CI 0.82-0.95), respectively (P<0.005). The sensitivity, specificity, PPV, and NPV of BALF Aspergillus galactomannan (GM) detection in the CPA group were 66.67%, 89.80%, 83.87%, and 77.19%, respectively, and the AUC was 0.94 (95% CI 0.89-0.99) (P<0.005). When combining BALF GM and BALF PCR detection, the sensitivity, specificity, PPV, and NPV were 92.31%, 89.80%, 87.80%, and 93.62%, respectively. CONCLUSION The BALF PCR detection method has good diagnostic value for CPA and combining this method with BALF GM detection can improve diagnostic sensitivity and specificity.

Feng Ye

Peiling Zeng

Zhengtu Li

Chunmei Tang

Wenkuan Liu

Danhong Su

Yangqing Zhan

Shaoqiang Li

Detection of Aspergillus DNA in BALF by Real-time PCR and Galactomannan Antigen for the Early Diagnosis of Chronic Pulmonary Aspergillosis.

实时PCR和半乳甘露聚糖抗原检测BALF中曲霉菌DNA用于慢性肺曲霉病的早期诊断。

OBJECTIVE MicroRNAs (miRNAs) have been used as molecular markers for various diseases. This study aimed to evaluate the predicted performance of miRNAs in fetal umbilical cord blood for detecting congenital heart disease (CHD). METHODS In this retrospective cohort study, a total of 60 pregnant women (involving 30 fetuses with CHD and 30 normal fetuses requiring induction of labor) were included. Umbilical cord blood was collected for miRNA measurement. Expression levels of the miRNAs were detected by qRT-PCR. The predictive accuracy of miRNA was assessed by constructing a receiver operating characteristic (ROC) curve and evaluated by calculating the area under the curve (AUC). The point biserial correlation coefficient (PBCC) was analyzed to evaluate the correlation of miRNA with CHD. RESULTS The CHD group and control group were well-balanced in age, gravidity, and parity. miRNA-133 was not detected in all subjects. Subjects with CHD fetuses had significantly lower levels of miRNA-1, miRNA-208, and miRNA-499. Different types of CHD showed different variation trends of miRNA expression. Correlation analysis showed that expression levels of miRNA-1, miRNA-208, and miRNA-499 were negatively correlated with the occurrence of CHD, with a PBCC of -0.65, -0.47, and -0.60, respectively. miRNA-1, miRNA-208, and miRNA-499 displayed an AUC of 0.86 (95% CI, 0.76-0.96; p<0.001), 0.75 (95% CI, 0.63-0.87; p=0.009), and 0.84 (95% CI, 0.74-0.95; p<0.001), respectively, for discriminating CHD from normal fetuses, with cut-off values of 0.795, 0.835, and 0.795, respectively. CONCLUSION The expression levels of miRNA-1, miRNA-208, and miRNA-499 in umbilical cord blood may be useful for predicting fetal CHD. The findings indicated that miRNAs have the potential to be a prenatal screening tool in the early diagnosis of CHD.

Dexuan Kong

Huidong Li

Chenchun Ren

Weiwei Yang

Zhikun Zhang

MicroRNAs in Fetal Umbilical Cord Blood as a Prenatal Screening Tool for Congenital Heart Disease.

胎儿脐带血中的微小RNA作为先天性心脏病的产前筛查工具。

Abbreviation	Ann. Clin. Lab. Sci.
Journal Impact	1.15
Quartiles(Global)	MEDICAL LABORATORY TECHNOLOGY(Q4)

ISSN	0091-7370, 1550-8080
h-index	62

Publication Information	Publisher: Association of Clinical Scientists，Publishing cycle: Bimonthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1971，Proportion of original research papers: 96.43%，Self Citation Rate:9.10%， Gold OA Rate: 0.32%
Average review cycle	网友分享经验：较慢,6-12周
Average recruitment ratio	网友分享经验：容易

Annals of Clinical and Laboratory Science

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