Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

{L-End}Objective To analyze the changes of seven potential biomarkers in plasma of patients with occupational silicosis (hereinafter referred to as "silicosis"), and explore their clinical value in determining the stage of silicosis. {L-End}Methods A total of 100 male silicosis patients were selected as the silicosis group (63 cases in stage Ⅰ and 37 cases in stage Ⅱ subgroups), and 100 male healthy individuals were selected as the control group using the 1∶1 matched case-control study. Enzyme-linked immunosorbent assay was used to analyze the level of interleukin-17 (IL-17), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), Krebs von den Lungen-6 (KL-6), connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), and histone H4 in plasma. Their clinical value for diagnosing silicosis was evaluated using receiver operating characteristic (ROC) curve, discriminant analysis stepwise method, and Fisher discriminant function analysis. {L-End}Results The levels of IL-17, MCP-1, MMP-9, KL-6, CTGF, PDGF, and histone H4 in the plasma of the silicosis group, silicosis stage Ⅰ subgroups, and stage Ⅱ subgroups were higher than those in the control group (all P<0.05). The levels of IL-17, MCP-1, and MMP-9 in the plasma of the stage Ⅱ subgroup decreased (all P<0.05), while the levels of KL-6, CTGF and histone H4 increased (all P<0.05) compared with the stage Ⅰ subgroup. The area under the ROC curve for diagnosing silicosis using these seven potential biomarkers ranged from 0.761 to 1.000 (all P<0.01), with the sensitivity of 0.640-1.000, the specificity of 0.840-0.990, and the Youden index of 0.540-0.990. The Fisher discriminant function was formed by stepwise discriminant analysis, and the results showed that the coincidence rate was 99.5%, and the misdiagnosis rate was 0.5% for diagnosing and staging silicosis with these seven potential biomarkers. The coincidence rate of diagnosing control group, silicosis stageⅠsubgroup and the silicosis stage Ⅱ subgroup was 100.0%, 98.4% and 100.0%, respectively. {L-End}Conclusion IL-17, MCP-1, MMP-9, KL-6, CTGF, PDGF and histone H4 in plasma can be used as biomarkers for the diagnosis of silicosis, and the Fisher discriminant function based on the combination of these seven biomarkers can assist in staging silicosis.

Whether direct manipulation of Parkinson's disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6-10 months), and thus provides a practical transgenic monkey model for future PD studies.
Animals ; Brain ; CRISPR-Cas Systems/genetics* ; Dependovirus/genetics* ; Haplorhini ; Phenotype ; Protein Kinases/genetics*

Whether direct manipulation of Parkinson’s disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6–10 months), and thus provides a practical transgenic monkey model for future PD studies.

The antigen of cluster of differentiation CD200 is widely expressed in hematological malignancies, and is of great significance for the diagnosis, monitoring of minimal residual disease and prognosis evaluation of B cell lymphoproliferative disorders, multiple myeloma and acute leukemia. In addition, CD200 plays an important regulatory role in tumor immune tolerance, suggesting that CD200 is a potential molecular target for the immunotherapy of hematological malignancies.

Objective:To evaluate the performance of Hybribio human papillomavirus (HPV) typing test kit for high risk HPV-DNA typing detection in screening of cervical precancer lesions.Methods:A total of 9 914 women were recruited in Henan, Shanxi, and Guangdong provinces from June to July 2017. All women underwent HPV DNA test. The women who diagnosed as HPV positive and cytological examination ≥ atypical squamous cells of undetermined significance (ASCUS) or HPV negative and cytological examination≥low-grade squamous intraepithelial lesions (LSIL) underwent colposcopy biopsy and pathological examination. Using the pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence interval ( CI) of high-risk HPV and HPV16/18 tests were calculated. Results:The mean age of 9 914 subjects was (45.0±9.3) years old. Among them, 1 302 subjects were detected as high risk HPV positive, including 211 of HPV16 positive and 64 of HPV18 positive. According to the pathological gold standard of cervical intraepithelial neoplasia grade 2 (CIN2) or worse, the sensitivity and specificity of high risk-HPV and HPV 16/18 for triaging ASCUS women were 90.6% (95% CI: 75.8%-96.8%) and 78.0% (95% CI: 74.5%-81.2%) as well as 56.3% (95% CI: 39.3%-71.8%) and 95.7% (95% CI: 93.8%-97.1%), respectively. The sensitivity and specificity of high risk-HPV and HPV 16/18 for cervical precancer lesions screening were 95.1% (95% CI: 88.1%-98.1%) and 87.6% (95% CI: 86.9%-88.2%) as well as 65.9% (95% CI: 55.1%-75.2%) and 97.8% (95% CI: 97.5%-98.1%), respectively. Conclusions:The Hybribio HPV test kit has a relative high sensitivity and specificity for cervical precancer lesions screening and ASCUS triaging. It is reliable for HPV DNA detection and cervical cancer screening.

Objective:To evaluate the performance of Hybribio human papillomavirus (HPV) typing test kit for high risk HPV-DNA typing detection in screening of cervical precancer lesions.Methods:A total of 9 914 women were recruited in Henan, Shanxi, and Guangdong provinces from June to July 2017. All women underwent HPV DNA test. The women who diagnosed as HPV positive and cytological examination ≥ atypical squamous cells of undetermined significance (ASCUS) or HPV negative and cytological examination≥low-grade squamous intraepithelial lesions (LSIL) underwent colposcopy biopsy and pathological examination. Using the pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence interval ( CI) of high-risk HPV and HPV16/18 tests were calculated. Results:The mean age of 9 914 subjects was (45.0±9.3) years old. Among them, 1 302 subjects were detected as high risk HPV positive, including 211 of HPV16 positive and 64 of HPV18 positive. According to the pathological gold standard of cervical intraepithelial neoplasia grade 2 (CIN2) or worse, the sensitivity and specificity of high risk-HPV and HPV 16/18 for triaging ASCUS women were 90.6% (95% CI: 75.8%-96.8%) and 78.0% (95% CI: 74.5%-81.2%) as well as 56.3% (95% CI: 39.3%-71.8%) and 95.7% (95% CI: 93.8%-97.1%), respectively. The sensitivity and specificity of high risk-HPV and HPV 16/18 for cervical precancer lesions screening were 95.1% (95% CI: 88.1%-98.1%) and 87.6% (95% CI: 86.9%-88.2%) as well as 65.9% (95% CI: 55.1%-75.2%) and 97.8% (95% CI: 97.5%-98.1%), respectively. Conclusions:The Hybribio HPV test kit has a relative high sensitivity and specificity for cervical precancer lesions screening and ASCUS triaging. It is reliable for HPV DNA detection and cervical cancer screening.

Objective To explore and study the effect of bundles on prevention and treatment of oral mucositis caused by chemoradiotherapy for patients with nasopharyngeal carcinoma. Methods A total of 40 patients who met the inclusion criteria from June 2014 to December 2014 were selected as the control group, who adopted routine nursing measures, 40 patients who met the inclusion criteria from January 2015 to June 2015 were assigned to the observation group. Bundles on prevention and treatment of oral mucositis caused by chemoradiotherapy for patients with nasopharyngeal carcinoma were edited using a series of evidence-based approach, and it was used to manage the patients of observation group. Results While doing 21, 28, 33 friction of radiotherapy, the oral mucositis level of 0 degree, Ⅰ degree,Ⅱ degree,Ⅲ degree and Ⅳ degree of the observation group were 8, 25, 7, 0, 0 cases;3, 11, 24, 2, 0 cases;0, 19, 13, 6, 2 cases respectively, which were lower than the control group whose degrees were 0, 31, 6, 3, 0 cases;0, 18, 11, 10, 1 cases;0, 9, 17, 9, 5 cases. The difference between the two groups was statistically significant (Z=-4.440,-3.441,-2.232, all P < 0.05 or 0.01). While doing 21, 28, 33 friction of adiotherapy, the throat pain level of 0 degree, Ⅰ degree,Ⅱ degree,Ⅲ degree of observation group were 4, 31, 5, 0; 2, 22, 14, 2; 0, 26, 12, 2 cases respectively, which were lower than the control group whose degrees were 1, 22, 16, 1 cases; 0, 10, 23, 7 cases; 0, 10, 17, 13 cases. The difference between the two groups was statistically significant (Z=-3.137,-3.326,-3.518, all P<0.01). While doing 28, 33 friction of radiotherapy, the Self Rating Anxiety Scale of the observation group scored 56.76 ± 3.19, 58.72 ± 5.41, which were lower than 60.58 ± 2.46, 63.42 ± 4.97 in the control group. The difference between the two groups was statistically significant (t=11.746, 10.561, all P <0.01). While doing 33 friction of radiotherapy, the self rating anxiety scale of the observation group was 60.56 ± 3.73, which was lower than 63.43 ± 4.77 in the control group. The difference between the two groups was statistically significant (t=-4.983, P<0.01). The following entries:swallow, sensation, eating in public, dry mouth, sticky saliva, feel sick of the quality of life questionnaire of the observation group were higher than the control group while doing 33 friction of radiotherapy. All the differences were statistically significant (t=-3.873-5.130, P<0.05 or 0.01). Conclusions The bundles could effectively prevent and treat oral mucositis caused by chemoradiotherapy for patients with nasopharyngeal carcinoma. It could release the throat pain, anxiety and depression of the patients, as well as improve the quality of life to some extent.

Objective To explore the impact of morphological changes of mitral valve coaptation on ischemic mitral regurgitation (IMR),and observe coaptation image of mitral valve in systole in patients with IMR by using real-time three-dimensional transesophageal echocardiography (RT3D-TEE).Methods RT3D-TEE was performed on 112 patients with IMR and 38 patients without MR as the control.Patients with IMR were divided into group of mild IMR (n =46),group of moderate IMR (n =45) and group of severe IMR (n =21),according to the severity of mitral regurgitation.Mitral valve quantification (MVQ)software of Qlab 8.1 was used for image post-processing of RT3D-TEE.The coaptation parameters was measured,included length of anterior combination(LCA3dlf),length of posterior combination(LCP3dlf),area of anterior combination(A3DTANT) and area of posterior combination (A3DTPOST) at end-systole.Then,these coaptation parameters of mitral valve were compared statistically.Logistic regression assessing was applied for analyzing the results.Results Coaptation line of anterior and posterior leaflets was almost same in normal subjects.With increasing of mitral regurgitation,a tendency to prolong in LCA3dlf and LCP3dlf were observed in IMR (P ＜0.05).Compared to that in mild and moderate IMR groups,besides A3DTANT and A3DTPOST,LCA3dlf and LCP3dlf were also increased significantly in severe IMR group (P ＜0.05).LCP3dlf was an independent correlation factor of IMR by Logistic regression analysis.The sensitivity was 73.3％ and the specificity was 94.7％ when LCP3dlf≥32 mm was regarded as cut-off point,and the area under the ROC curve was 0.949 (0.900～0.999).Conclusions Abnormal coaptation of anterior and posterior leaflets of mitral valve might be one of main cause of IMR.Involution structure of mitral valve before surgery is helpful for surgeon to select an optical surgical procedure and evaluate effects of treatment in patients with IMR.

Objective:To explore the changes of saliva urea, creatinine (Cr), and uric acid (UA) before and after hemodialysis in patients with end-stage renal disease (ESRD), and to evaluate the clearing effect of Urea, Cr, and UA.
Methods:Saliva and serum (2 mL) were collected from the dialysis patients. The concentrations of Urea, Cr, and UA in both samples were measured by biochemical analyzer. The concentrations of Urea, Cr, and UA in the saliva and the serum, and their correlation were analyzed. Before and after the hemodialysis, the reduction ratio (RR) of Urea, Cr, and UA in the saliva and the serum was calculated.
Results:In ESRD dialysis patients, the levels of Urea, Cr, and UA in the saliva and the serum were highly correlated (correlation coeffcients were 0.979, 0.973, and 0.948, respectively). The concentrations of Urea, Cr, and UA in the saliva and the serum before the dialysis were lower than those after the dialysis, with signiifcant difference (P<0.05). The RR of Urea, Cr, and UA in the saliva and the serum did not differ statistically (P>0.05).
Conclusion:The clearing effect of salivar Urea, Cr, and UA is similar to that of the serum. Saliva is expected to replace the serum to evaluate hemodialysis efficacy and monitor the renal disease in ESRD patients.