Objective To investigate the relationship between pulse wave velocity and cardiovascular risk factors in prehypertensive subjects. Methods We selected 195 normotensives and divided them into two groups, which was 90 subjects with optimal blood pressure(BP

Objective To explore the expression and mechanisms of MMP-9 in vascular remodeling of two-kidney and one-cliped hypertension rats. Methods Male Wistar rats were randomly divided into sham operation group( n = 10), two-kidney and one-clip model (2KIC) group ( n = 10) and telmisartan group ( n = 7 ). Telmisartan group were injected with telmisartan every day. The blood pressure was determined every week. The morphologic change of carotid artery and thoracic aorta was observed with HE stainning 8 weeks after treatment with telmisartan.Arteries was performed to evaluate the expression of MMP-9 with immunohistochemisty. Results The blood pressure,vessel wall,and the expression of MMP-9 in model group were significantly higher than that of control group.Telmisartan nearly normalized arterial pressure and suppressed all these changes. Conclusion MMP-9 was related to vascular remodeling and Telmisartan could regulate vascular remodeling in 2-kidney and 1-cliped hypertension rats by inhibiting the pathway of MMP-9.

Objective: To investigate whether plasma microRNAs has-let-7d and has-let-7e can be used as potential molecular markers for workers with occupational exposure to mercury. Methods: October 2013, the workers with occupational exposure to mercury who worked in a mercury thermometer factory and participated in occupational health examination were selected as subjects, and biological samples and basic data were collected. The subjects were divided into chronic mercury poisoning group,mercury absorption group,and control group,with 30 individuals in each group. AmicroRNA microarray combined with RT-qPCR was used to measure the expression of has-let-7d and has-let-7e in the three groups, the receiver operating characteristic(ROC)curve was used to analyze the values of has-let-7d and has-let-7e in the diagnosis of occupational chronic mercury poisoning,a software platform was used to predict target genes. Gene ontology enrichment analysis and KEGG pathway analysis were also performed. Results: Compared with the control group, the chronic mercury poisoning group and the mercury absorption group had significant increases in the expression of has-let-7d and has-let-7e(P<0.05). The areas under the ROC curve for microRNAs has-let-7d and has-let-7e in the diagnosis of occupational chronic mercury poisoning were 0.912(95% confidence interval[CI]0.843-0.981)and 0.908(95%CI0.837-0.979),respectively,and there was a significant difference between them(P<0.001). Conclusion Plasma microRNAs has-let-7d and has-let-7e can be used as potential molecular markers for workers with occupational exposure to mercury.

Female ; Hearing Disorders ; etiology ; Hearing Tests ; Humans ; Infant, Newborn ; Male ; Neonatal Screening ; Risk Factors

Objective: To investigate the clinicopathologic and molecular features of the rare cribriform morular variant of papillary thyroid carcinoma (CMV-PTC). Methods: The clinicopathologic data of 10 patients with CMV-PTC were retrospectively reviewed. Immunohistochemical (IHC) staining was done using LSAB method. DNA sequencing for APC were applied using Sanger method. BRAF V600E mutation was examined using ARMS method. The cytological, morphological, IHC and molecular features were analyzed. Results: All patients were female at an average age of 27 years old. The tumors were mostly located in the right lobe of thyroid. Fine needle aspiration cytology was performed in three patients; two were diagnosed as suspicious for PTC and one as PTC. Nine tumors presented as solitary nodule and two as multiple nodules in both lobes. Infiltration was demonstrated in three cases. The average size was 2.6 cm. The neoplastic cells were arranged in papillary, cribriform, solid and glandular patterns, with rare or without colloid inside the lumen. The number of morula varied, ranging from zero to many. The neoplastic cells were variably enlarged, showing round, oval or spindle shape. Nuclear irregularity was identified as irregular membrane, nuclear grooves or pseudoinclusion, but no typical ground glass feature. Peculiar nuclear clearing could be observed in the morular cells. IHC staining showed the neoplastic cells were negative for thyroglobulin and p63, but positive for TTF1, cytokeratin 19 and estrogen receptor. Diffuse staining with cytokeratin was seen in the neoplastic cells and the morula. Specific cytoplasmic and nuclear staining of β-catenin was seen in the neoplastic cells but not the morula. Ki-67 proliferation index was 1%-30%. No recurrence or metastasis was observed. One patient was demonstrated to harbor both somatic and germline mutations of the APC gene, who was found to have adenomatous polyposis and her mother died of colonic carcinoma. No BRAF V600E mutation was detected. Conclusions CMV-PTC is rare and shows atypical cytological and clinicopathological features, and it is easily misdiagnosed.TG, TTF1, ER and β-catenin are specific IHC markers for CMV-PTC. The morula is negative for cytokeratin 19, in contrast to squamous metaplasia. Although CMV-PTC has indolent clinical behavior, a definite diagnosis is necessary to rule out the possibility of APC gene mutation and related extra-thyroidal neoplasm, such as FAP and Gardner syndrome.

This study investigated the association of apolipoprotein A5 (apoAS) gene polymorphism at position -113 ITC with cerebral infarction in patients with type 2 diabetes. A total of 256 type 2 diabetic patients without cerebral infarction (T2DM), 220 type 2 diabetic patients with cerebral infarction (T2DMCI) and 340 healthy subjects were recruited from the same region (Hubei province,China). The genotype of apoA5 -1131TC was analyzed by polymerase chain reaction, followed by restriction fragment length polymorphism (PCR-RFLP). Total cholesterol, HDL cholesterol,LDL-cholesterol and trigiycerides were quantitatively detected by using standard enzymatic techniques. The results showed that the prevalence of the apoA5 -1131C allele was significantly higher in T2DMCI group than that in control group (42.7% versus 31.2%, P<0.01). The carriers of rare C allele had higher TG levels as compared with carders of common allele in the three groups (P<0.01). Logistic regression models, which were adjusted for age, gender, blood pressure, BMI, FBS, smoking,LDL-C and HDL-C, revealed that patients carrying the apoA5 -1131C allele and CC homozygotes were at high risk for T2DMCI. It was concluded that the apoA5 -ll31C allele variant is an independent genetic risk factor for T2DMCI.

Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression.Oncogenes promote cell growth and proliferation,whereas tumor suppressor genes inhibit cell growth and division.The dysregulation of these genes can lead to the development of cancer.Recent studies have focused on non-coding RNAs(ncRNAs),including circular RNA(circRNA),long non-coding RNA(lncRNA),and microRNA(miRNA),as therapeutic targets for cancer.In this article,we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets.Here,we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment.Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.

Objective: To investigate the role of p75 neurotrophin receptor (p75NTR) in the irradiation-induced hippocampal neurogenesis impairment. Methods: Thirty Sprague-Dawley rats were subject to whole brain irradiation with a single dose of 10 Gy 4 MeV electron beam. At 1 month after irradiation, the hippocampal tissues of the rats were collected. Western blot was used to detect the changes in the expression level of p75NTR protein. Immunofluorescence confocal laser microscopy was performed to observe the variations in the hippocampal neurogenesis. The stereotatic method was adopted for intra-hippocampal injection of AAV-shp75NTR to specifically knock out p75NTR.The relationship between p75NTR and hippocampal neurogenesis was analyzed. Results: Western blot demonstrated that the expression of p75NTR protein was significantly up-regulated by 43.8% after irradiation (P<0.05). Immunofluorescent staining showed that the quantity of BrdU⁺ NeuN⁺ cells in rats was significantly decreased by 81.5% at 1 month after irradiation compared with that in the control group (P<0.01). After the specific knockout of p75NTR, hippocampal neurogenesis was obviously protected. Conclusion p75NTR plays a pivotal role in the irradiation-induced hippocampal neurogenesis impairment.

ObjectiveTo investigate the possible mechanism of Bushen Zhuyun prescription （BSZYP） to reduce the level of ovarian apoptosis in Brown Norway （BN） rats with luteal phase deficiency （LPD）. MethodFifty SPF female BN rats were randomly divided into a model group， a dydrogesterone group （0.002 g·kg^-1）， and a low （4.5 g·kg^-1）， a medium （9 g·kg^-1）， and a high-dose （18 g·kg^-1） BSZYP groups， with ten rats in each group. The rats were administrated with corresponding drugs by gavage， once a day for three estrus cycle. Western blot was used to detected the protein expression levels of c-Jun NH2 terminal kinase （JNK）， extracellular signal-regulated kinase （ERK）， phosphorylated-ERK （p-ERK）， phosphorylated-JNK （p-JNK）， p38 mitogen-activated protein kinase （p38 MAPK）， phosphorylated-p38 MAPK （p-p38 MAPK ）， B-cell lymphoma （Bcl-2）， and Bcl-2 associated X protein （Bax） in ovary. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of ERK， JNK， p38 MAPK， Bax， and Bcl-2 in ovary. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum progesterone （P） and estradiol （E₂） levels. Hematoxylin-eosin （HE） staining was used to observe the ovarian tissue morphology. ResultCompared with the model group， the recovery of estrus cycle of rats in all BSZYP groups had statistical significance after 1-circle administration （P<0.05）. The ovarian tissue morphology in the low-dose BSZYP group was improved， and that in the medium and high-dose BSZYP groups was significantly improved with clear follicle， less vesicular follicle and atretic follicle， and more granular layers. The number of luteum， especially the fresh luteum， in the medium and high-dose groups was increased with smooth edge and large volume. The mRNA expression level of Bcl-2 was increased in all-dose BSZYP groups， while the mRNA expression level of Bax was significantly decreased in all-dose BSZYP group （P<0.05， P<0.01）. The mRNA expression levels of JNK and p38 MAPK were significantly decreased in the high-dose BSZYP group （P<0.01）， and the mRNA expression levels of ERK were increased in the low and medium-dose BSZYP groups （P<0.05）. The protein expression level of Bcl-2 was significantly increased in the medium and high-dose BSZYP groups （P<0.01）， and the protein expression level of Bax was significantly decreased in the all-dose BSZYP groups （P<0.01）. No significant difference was observed in the protein expressions of JNK， ERK， and p38 MAPK in the BSZYP groups. The protein expression levels of p-ERK in the ovarian tissues of rats were significantly inoreased in the medium and high-dose BSZYP group （P<0.01）， p-JNK， and p-p38 MAPK in the ovarian tissues of rats were significantly decreased in the medium and high-dose BSZYP group （P<0.01）. The level of E₂ was increased in all-dose BSZYP groups （P<0.05， P<0.01）， and the level of P in the medium-dose BSZYP group was increased （P<0.05）. ConclusionBSZYP improved the serum sex hormones， restored the estrous cycle， reduced atretic follicle and vesiculation， and maintained luteal morphology and function of BN rats， so as to improve luteal function and treat luteal phase deficiency. The mechanism of BSZYP may be related to reduce the level of ovarian tissue apoptosis in BN rats by regulating MAPKs signaling pathway.

MicroRNAs (miRNAs) are small noncoding RNAs that have a pivotal role in the post-transcriptional regulation of gene expression by sequence-specifically targeting multiple mRNAs. Although miR-33a was recently reported to play an important role in lipid homeostasis, atherosclerosis, and hepatic fibrosis, the functions of miR-33a in tumor progression and metastasis are largely unknown. Here, we found that downregulated miR-33a in breast cancer tissues correlates with lymph node metastasis. MiR-33a expression is significantly lower in the highly metastatic breast cancer cell lines than the noncancerous breast epithelial cells and non-metastatic breast cancer cells. Moreover, the overexpression of miR-33a in metastatic breast cancer cells remarkably decreases cell proliferation and invasion in vitro and significantly inhibits tumor growth and lung metastasis in vivo, whereas its knockdown in non-metastatic breast cancer cells significantly enhances cell proliferation and invasion in vitro and promotes tumor growth and lung metastasis in vivo. Combining bioinformatics prediction and biochemical analyses, we showed that ADAM9 and ROS1 are direct downstream targets of miR-33a. These findings identified miR-33a as a negative regulator of breast cancer cell proliferation and metastasis.
ADAM Proteins ; deficiency ; genetics ; Animals ; Breast Neoplasms ; genetics ; pathology ; Cell Line, Tumor ; Cell Movement ; genetics ; Cell Proliferation ; genetics ; Female ; Humans ; Lung Neoplasms ; secondary ; Membrane Proteins ; deficiency ; genetics ; Mice ; MicroRNAs ; genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Protein-Tyrosine Kinases ; deficiency ; genetics ; Proto-Oncogene Proteins ; deficiency ; genetics