Aim To investigate the effect of small inter-ference RNA-mediated silcencing of the Bmi-1 gene on cell invasion and metastasis in human nasopharyngeal carcinoma cell line CNE-1 . Methods Chemically syn-thesized siRNA targeting the Bmi-1 gene was transfect-ed into CNE-1 cells, which had high invasive and me-tastatic potential. The expression of Bmi-1 mRNA and protein were detected by quantative Real-time PCR and Western blot, respectively. The effects of Bmi-1 knockdown on CNE-1 cells migration and invasion were analysied by Transwell migration assay and Matrigel in-vasion assay. Results Transfected with Bmi-1 siRNA significantly down-regulated the expression of Bmi-1 mRNA and protein as compared with the control group. CNE-1 cells transfected with Bmi-1 siRNA had lower levels of invasion and migration capacity than cells in the control group. Conclusion SiRNA-media-ted silencing of the Bmi-1 gene could significantly in-hibit cell migration and invasion in human nasopharyn-geal carcinoma cell line CNE-1 .

Objective：To explore the difference in creative thinking and the related factors between deaf children and normal children.Methods：Observation group(n=122)with the hearing disability students were selected from 4 special education schools.Control group(n=122)was come from 2 ordinary primary schools and 2 ordinary middle schools.The two groups were given both the New Creativity Test and the Combined Raven's Test.Results：(1)Deaf children got lower scores than normal children in verbal fluency[(7.76±0.75)vs.(12.98±0.59),P<0.001],verbal flexibility[(4.28±0.33)vs.(7.87±0.28),P<0.001],verbal originality [(7.16±0.89)vs.(11.35±0.72),P<0.001],figural flexibility[(9.69±0.35)vs.(11.10±0.31),P=0.003]and IQ[(101.05±1.196)vs.(105.01±1.102),P=0.030].Deaf children got higher scores than normal children in figural elaboration[(3.24±0.40)vs.(1.96±0.22),P=0.006].There was no significant difference in fluency and originality of figural task between the two groups.(2)Deaf children's scores of verbal fluency and verbal originality were positively correlated with their age(β=0.310,0.301;Ps<0.01).Deaf children's scores of verbal flexibility were positively correlated with length of bilingual education(β=0.308,P<0.001).Deaf children's scores of figural fluency,figural flexibility,figural originalityand figural elaboration were correlated positively with their age of sign language(β=0.321,0.308,0.228,0.456;Ps<0.05).Conclusions:(1)Deaf children are lower than normal children in verbal fluency,verbal flexibility,verbal originality,figural flexibility,and are higher in figural elaboration.There is no difference in figural fluency and originality between them.(2)Sign language is a major related factor to deaf children's figural creative thinking.

OBJECTIVE To investigate the significance of CNS in clinical infections.METHODS A total of 114 CNS strains isolated from our hospital were identified by conventional procedures and the icaD gene was amplified by PCR.RESULTS Of all CNS strains,the highest isolated rate was S.epidermidis(41.2%).CNS isolated from deep venous catheters,wound secretions and blood had a higher rate of carrying ica operon,accounted for 44.4%,42.1% and 36.8%,respectively,whereas 24.0% in respiratory secretions and 14.1% in urine.Among the ica operon positive CNS strains,the percentages of S.epidermidis and S.haemolyticus were 42.6% and 19.0%.CONCLUSIONS There is a wide range of CNS species carrying ica operon,especially in S.epidermidis.CNS isolated from different specimens might have different significances.It should be cautious to assess the results of isolated CNS from respiratory and urine specimens.The CNS isolates from blood specimens might be contaminated.The PCR method for the ica operon is simple and easy.

Objective To evaluate the sensitivity and specificity of different HbA1C cutoff points for diabetes diagnosis in high risk outpatients in Harbin.Methods A total of 2 122 high risk outpatients(male 1 032 and female 1 090)for diabetes screening in the Fourth affiliated Hospital of Harbin Medical University from April 2013 to February 2015 were included in this study, with the average age of(49.26±13.00)year. Oral glucose tolerance tests(OGTT)were conducted and HbA1C levels were examined in these patients. The sensitivity and specificity of different HbA1C cutoff points were calculated and a receiver operator characteristic(ROC)curve was then built.Results The average level of HbA1C in these subjects was(6.45±1.72)%. The prevalence of diabetes was 41.85%. The area under ROC curve(AUC)was 0.89 with the optimal cutoff point of HbA1C 6.0% and 0.68 for the highest Yonden index. The sensitivity and specificity of HbA1C 6.0% were 84.01% and 83.67% respectively. The sensitivity and specificity of HbA1C 6.5% were 62.84% and 95.92%, respectively. The AUC of HbA1C≥6.5% was 0.732. Conclusion HbA1C works well as the diagnostic standard for diabetes in high risk outpatients of Harbin city. The cutoff point of HbA1C 6.0% is suitable for screening diabetes in high risk population, and HbA1C 6.5% is appropriate for diabetes diagnosis, with high sensitivity and specificity.

Objective:To explore the key points and implementation of establishing a whole-process clinical research management system.Methods:Based on the problems in practice, combined with project management experiences, this article analyzed the construction of the whole-process clinical research management system.Results:The establishment of the management system provides a comprehensive and sustainable safeguard for clinical research, as well as the improvement of efficiency and quality of clinical research.Conclusions:The establishment of an effective whole-process management system for clinical research project is a useful exploration of the research service model in China.

Objective:To analyze the differential genes and related signaling pathways of microglia subpopulations in Parkinson's disease (PD) -like mouse brains induced by paraquat (PQ) based on single-cell RNA sequencing, and provide clues to elucidate the mechanism of PQ-induced PD-like changes in the brain of animals.Methods:In September 2021, six male 6-week-old C57BL/6 mice were randomly divided into control group and experimental group (three mice in each group) . The mice were injected with saline, 10.0 mg/kg PQ intraperitoneally, once every three days, and 10 consecutive injections were used for modeling. After infection, the brains of mice were taken and 10×Genomics single-cell RNA sequencing was performed. Microglia subpopulations were screened based on gene expression characteristics, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The differential genes of microglia subpopulations between the experimental group and control group were further screened, and functional enrichment analysis was performed using bioinformatics tools. Mouse microglia (BV2 cells) were treated with 0, 60, 90 μmol/L PQ solution, respectively. And real-time fluorescence quantitative PCR experiments were conducted to validate the expressions of differential genes hexokinase 2 (Hk2) , ATPase H+ Transporting V0 Subunit B (Atp6v0b) and Neuregulin 1 (Nrg1) .Results:Cluster 7 and Cluster 20 were identified as microglia subpopulations based on the signature genes inositol polyphosphate-5-phosphatase d, Inpp5d (Inpp5d) and transforming growth factor beta receptor 1 (Tgfbr1) , and they reflected the microglia-activated M2 phenotype. The bioinformatics analysis showed that the characteristic genes of identified microglia subpopulations were enriched in endocytosis. In terms of molecular function, it mainly enriched in transmembrane receptor protein kinase activity and cytokine binding. The up-regulated genes of Cluster 7 were mainly enriched in lysosomal pathway, endocytosis pathway, and down-regulated genes were mainly enriched in neurodegenerative disease and other signaling pathways. The up-regulated genes of Cluster 20 were mainly enriched in signaling pathways related to PD, and down-regulated genes were mainly enriched in cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathways, neurological development, synaptic function and other signaling pathways. The results of real-time fluorescence quantitative PCR showed that the expressions of Hk2 mRNA and Atp6v0b mRNA increased and the expression of Nrg1 mRNA decreased in the 90 μmol/L PQ-treated BV2 cells compared with the 0 μmol/L, and the differences were statistically significant ( P<0.05) . Conclusion:Microglia are activated in the PQ-induced PD-like mouse model and polarized toward the M2 phenotype. And their functions are associated with lysosomal (endocytosis) , synaptic functions and the regulation of PD-related pathways.

Objective:To analyze the differential genes and related signaling pathways of microglia subpopulations in Parkinson's disease (PD) -like mouse brains induced by paraquat (PQ) based on single-cell RNA sequencing, and provide clues to elucidate the mechanism of PQ-induced PD-like changes in the brain of animals.Methods:In September 2021, six male 6-week-old C57BL/6 mice were randomly divided into control group and experimental group (three mice in each group) . The mice were injected with saline, 10.0 mg/kg PQ intraperitoneally, once every three days, and 10 consecutive injections were used for modeling. After infection, the brains of mice were taken and 10×Genomics single-cell RNA sequencing was performed. Microglia subpopulations were screened based on gene expression characteristics, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The differential genes of microglia subpopulations between the experimental group and control group were further screened, and functional enrichment analysis was performed using bioinformatics tools. Mouse microglia (BV2 cells) were treated with 0, 60, 90 μmol/L PQ solution, respectively. And real-time fluorescence quantitative PCR experiments were conducted to validate the expressions of differential genes hexokinase 2 (Hk2) , ATPase H+ Transporting V0 Subunit B (Atp6v0b) and Neuregulin 1 (Nrg1) .Results:Cluster 7 and Cluster 20 were identified as microglia subpopulations based on the signature genes inositol polyphosphate-5-phosphatase d, Inpp5d (Inpp5d) and transforming growth factor beta receptor 1 (Tgfbr1) , and they reflected the microglia-activated M2 phenotype. The bioinformatics analysis showed that the characteristic genes of identified microglia subpopulations were enriched in endocytosis. In terms of molecular function, it mainly enriched in transmembrane receptor protein kinase activity and cytokine binding. The up-regulated genes of Cluster 7 were mainly enriched in lysosomal pathway, endocytosis pathway, and down-regulated genes were mainly enriched in neurodegenerative disease and other signaling pathways. The up-regulated genes of Cluster 20 were mainly enriched in signaling pathways related to PD, and down-regulated genes were mainly enriched in cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathways, neurological development, synaptic function and other signaling pathways. The results of real-time fluorescence quantitative PCR showed that the expressions of Hk2 mRNA and Atp6v0b mRNA increased and the expression of Nrg1 mRNA decreased in the 90 μmol/L PQ-treated BV2 cells compared with the 0 μmol/L, and the differences were statistically significant ( P<0.05) . Conclusion:Microglia are activated in the PQ-induced PD-like mouse model and polarized toward the M2 phenotype. And their functions are associated with lysosomal (endocytosis) , synaptic functions and the regulation of PD-related pathways.

Objective To explore the mutation characteristics of DMD gene in patients with Duchenne or Becker muscular dystrophy and female carriers, to provide effective prenatal diagnosis. Methods Samples were collected from 94 male patients clinically diagnosed with Duchenne or Becker muscular dystrophy and 121 corresponding female relatives from Qingdao Women and Children′s Hospital from June 2011 to October 2018. Multiplex ligation-dependent probe amplification (MLPA) was used to detect their DMD gene, and 23 high risk pregnants were performed prenatal diagnosis. Any candidate of DMD gene single-exon deletion was validated by further PCR amplification. The sample with whole DMD gene deletion was confirmed by chromosomal microarray analysis (CMA) to detect copy number variations and break site. Results Among 94 clinical Duchenne or Becker muscular dystrophy patients, 66(70.2%, 66/94) were detected gene mutation; 56 cases were exon deletion mutation and 10 cases were duplication mutation. In 121 female relatives, 48 cases (39.7%, 48/121) were diagnosed as carriers. The mutation carrying rate, was 64.5% (40/62) identified in 62 mothers of Duchenne or Becker muscular dystrophy patients. Five Duchenne or Becker muscular dystrophy fetuses and 5 carrier fetuses were prenatally diagnosed in 23 high risk pregnants. Two children with the entire DMD gene deletion were identified more deletions at Xp21, with deletions of 6.66 Mb and 10.64 Mb respectively. Conclusions MLPA may be an important method to detect DMD gene mutation of deletion and duplication. Therefore, the diagnosis of probands, female carriers and making an effective prenatal diagnosis are essential to reduce the birth of children with Duchenne or Becker muscular dystrophy.

Objective:To compare the predictive value of the HEART, TIMI and GRACE scores for major adversecardiovascular events (MACEs) at 7 and 28 days in patients with actue non-ST-segment elevation myocardial infarction (NSTEMI).Methods:More than 12 000 patients with chest pain from the Emergency Department of Zhongshan Hospital Affiliated to Fudan University from October 2017 to October 2018 were studied, including 566 patients with cardiogenic chest pain, 105 patients with ST-segment elevation myocardial infarction (STEMI) excluded and 15 patients lost to follow-up. Finally, 109 patients with NSTEMI and 337 non-myocardial patients with cardiogenic chest pain were enrolled. NSTEMI patients were divided into subgroups according to whether MACEs occurred. LSD t-test, Mann-Whitney U test or χ2 test were used to analyze and compare the differences between the two subgroups about the baseline data, clinical data, HEART, TIMI and GRACE scores at the time of visit. Multivariate logistic regression analysis was used to explore the independent factors of MACEs at 7 and 28 days. And the predictive values of different scores for 7-day MACEs and 28-day MACEs were compared in NSTEMI patients through the receiver operating characteristic (ROC) curve. Results:Compared NSTEMI patients with non-myocardial patients with cardiogenic chest pain, we found a statistically significant differences in sex, past history of coronary heart disease,≥3 risk factors for atherosclerosis, electrocardiogram, high-sensitivity troponin T (hs-cTnT), creatinine value, past history of myocardial infarction, HEART score, TIMI score and GRACE score. In further subgroup analysis of NSTEMI patients who were divided according to whether MACEs occurred, we found previous history of stroke and increased hs-cTnT were statistically different in 7 days after the onset of the disease. The multivariate analysis showed that the previous history of stroke and increased hs-cTnT were independent factors for the occurrence of MACEs at 7 days after the onset of NSTEMI; The previous history of stroke and increased hs-cTnT, electrocardiogram ST segment depression and TIMI score were statistically different at 28 days after the onset of NSTEMI. The multivariate analysis showed that the previous history of stroke and TIMI score were independent factors for the occurrence of MACEs at 28 days after the onset of NSTEMI patients. ROC curve indicated that the predictive value of TIMI score (AUC=0.715, 95% CI: 0.482-0.948) was better than HEART (AUC=0.659, 95% CI: 0.414-0.904) and GRACE scores (AUC=0.587, 95% CI: 0.341-0.833)in predicting MACEs in NSTEMI patients. Conclusions:HEART score, TIMI score and GRACE score can be used to evaluate NSTEMI patients. There is an independent predictive value on TIMI score for the occurrence of 28-day MACEs in NSTEMI patients.

Objective:To investigate the effects of placenta previa on the surgical and pregnancy outcomes in patients with total/subtotal or segmental hysterectomy attributed to placenta accreta spectrum disorders (PAS).Methods:This study retrospectively enrolled 510 patients who gave birth and underwent total/subtotal hysterectomy or segmental hysterectomy (local implantation site) due to PAS at the third Affiliated Hospital of Guangzhou Medical University from January 1, 2017, to December 31, 2022. These subjects were divided into the placenta previa group (427 cases) and non-placenta previa group (83 cases). According to the type of hysterectomy, they were further divided into the total/subtotal hysterectomy and placenta previa subgroup (221 cases), total/subtotal hysterectomy and non-placenta previa subgroup (23 cases), segmental hysterectomy and placenta previa subgroup (206 cases), and segmental hysterectomy and non-placenta previa subgroup (60 cases). Nonparametric test or Chi-square test were used to compare the differences in the clinical features, surgical and pregnancy outcomes between different groups. Binary logistic regression was used to analyze the effects of placenta previa on the risk of additional surgical procedures and adverse maternal outcomes. Results:(1) Compared with the non-placenta previa group, the hemorrhage volume within 24 h postpartum [1 541 ml (1 036-2 368 ml) vs 1 111 ml (695-2 000 ml), Z=－3.91] and the proportion of women requiring additional surgical procedures [84.8% (362/427) vs 69.9% (58/83), χ2=10.61], with total/subtotal hysterectomy [51.8% (221/427) vs 27.7% (23/83), χ2=16.10], cystoscopy and/or ureteral stenting [60.7% (259/427) vs 31.3% (26/83), χ2=24.25], total adverse pregnancy outcomes [86.9% (371/427) vs 65.1% (54/83), χ2=17.75], hemorrhage volume>1 500 ml within 24 h postpartum [54.1% (231/427) vs 33.7% (28/83), χ2=29.94], transfusion of blood products [75.9% (324/427) vs 47.0% (39/83), χ2=28.27] were all higher in the placenta previa group (all P<0.05). Binary logistic regression analysis found that for PAS patients with hysterectomy, regardless of the hysterectomy type (total/subtotal/segmental), placenta previa was risk factor for requiring additional surgical procedures ( aOR=3.26, 95% CI: 1.85-5.72) and adverse pregnancy outcomes ( aOR=5.59, 95% CI: 2.01-6.42), even if adjusting for the confounding factors such as maternal age, number of previous cesarean sections, parity, gestational weight gain, twin pregnancy, and the use of assisted reproductive technology. (2) In patients with total/subtotal hysterectomy, the proportion of women requiring additional surgical procedures was higher in those with placenta previa [82.8% (183/221) vs 56.5% (13/23), χ2=9.11] than those without placenta previa, especially the proportion of cystoscopy and/or ureteral stenting [67.9% (150/221) vs 34.8% (8/23), χ2=9.99] (both P<0.05). However, no significant difference was found in adverse pregnancy outcomes [89.6% (198/221) vs 87.0% (20/23), χ2<0.01, P=0.972] between the two groups. In patients with segmental hysterectomy, higher proportions of women requiring additional surgery [86.9% (179/206) vs 75.0% (45/60), χ2=4.94], with adverse pregnancy outcomes [84.0% (173/206) vs 56.7% (34/60), χ2=25.31], cystoscopy and/or ureteral stenting [52.9% (109/206) vs 30.0% (18/60), χ2=9.78], vascular occlusion [94.2% (194/206) vs 71.7% (43/60), χ2=24.23], hemorrhage volume>1 500 ml within 24 h postpartum [46.6% (96/206) vs 23.3% (14/60), χ2=10.37], and transfusion of blood products [68.9% (142/206) vs 33.3% (20/60), χ2=24.73] were found in the placenta previa group (all P<0.05). Furthermore, patients with placenta previa had more hemorrhage volume within 24 h postpartum [1 368 ml (970-2 026 ml) vs 995 ml (654-1 352 ml), Z=－3.66, P<0.001] in the segmental hysterectomy subgroup. After adjusting for the confounding factors such as age, number of previous cesarean sections, parity, gestational weight gain, twin pregnancy, and the use of assisted reproductive technology, binary logistic regression analysis found that placenta previa did not increase the risk of additional surgical operations ( aOR=2.71, 95% CI: 0.99-7.42) and adverse pregnancy outcomes ( aOR=2.14, 95% CI: 0.54-8.42) in patients with total/subtotal hysterectomy but were risk factors of the two outcomes for those with segmental hysterectomy ( aOR=4.67, 95% CI: 2.15-10.10; aOR=3.80, 95% CI: 1.86-7.77). Conclusions:Placenta previa increases the risk of additional surgical procedures and adverse pregnancy outcomes in patients with total/subtotal or segmental hysterectomy caused by PAS. Appropriate preparation is required after the clinical diagnosis of PAS with placenta previa.