Digital language markers distinguish the pathological effect of Alzheimer′s disease and mild cognitive impairment from the aging effect / 中华神经科杂志

Objective:To characterize the digital language markers in Alzheimer′s disease (AD) and mild cognitive impairment (MCI) patients, and to explore the pathological effect and aging effect on these markers.Methods:AD ( n=14) and MCI ( n=16) patients from memory clinic in Peking Union Medical College Hospital, age-matched cognitively normal elderly adults ( n=18) and youthful adults ( n=19) as controls participated in the study. The digital speech data of animal fluency test were collected. Novel language markers such as response time, semantic similarity and word frequency were analyzed in addition to the traditional word production, clustering and switching indicators by trained professionals. Multiple linear regression analysis with multiple comparison was used to test the associations of language markers with the cognitive status, adjusting for education. Results:The results of multiple regression analysis showed that, after adjusting for the years of education, statistically significant differences existed in 11 language markers among the four groups ( P<0.001), except for the effective word production in the last 15 s, cluster size, the first word response time and the average semantic similarity. Compared to other three groups, AD group differed significantly in effective word production, effective rate, repetitive rate, effective word production in the first 15 s, the number of subcategories, single word production time and inter-subcategory switching interval ( P<0.001). In addition, compared to cognitively normal youthful group, AD group had less number of switching and shorter semantic maximum distance ( P=0.001, P<0.001); both AD and MCI groups had longer intra-subcategory switching interval ( P<0.001, P=0.001); AD, MCI and cognitively normal elderly groups had significantly higher word frequency ( P<0.001); MCI group had significantly less number of effective word production and subcategories ( P=0.002, P=0.003); both MCI and cognitively normal elderly groups had significantly longer single word production time ( P<0.001). Conclusions:The performance of AD patients on the semantic fluency test task was affected by both pathological effect and normal aging effect. Pathological indicators included effective word production, effective rate, repetition rate, effective word production in the first 15 s, the number of subcategories, inter-subcategory switching interval and single word production time. These results provide a new approach to identify the specific effects of AD dementia.

Analysis of MYOC gene variants among sporadic patients with primary open-angle glaucoma / 中华医学遗传学杂志

OBJECTIVE@#To screen for MYOC gene variants among sporadic patients with primary open angle glaucoma (POAG).@*METHODS@#For 398 patients with POAG, Sanger sequencing was applied to detect potential variants of the MYOC gene.@*RESULTS@#Eight patients (2.0%) were found to harbor variations of the MYOC gene. These included five types of variants, among which c.667C>T (p.Pro223Ser) and c.1138G>T (p.Asp380Tyr) were novel. c.382C>T (p.Arg128Trp), c.1109C>T(p.Pro370Leu) and c.1130C>A (p.Thr377Lys) were previously associated with POAG. Alignment of amino acid sequences of MYOC proteins of various species revealed that the two novel variants have occurred at highly conserved positions. c.1138G>T was predicted to be possible pathogenic by Bioinformatic analysis.@*CONCLUSION@#Two novel variants of the MYOC gene were detected among sporadic POAG patients, which enriched its variant spectrum.

Expression differences of poly adenosine diphosphate ribose polymerase 1 in the human intracranial ruptured and unruptured aneurysm walls / 中国脑血管病杂志

Objective To investigate the expression differences of poly adenosine diphosphate ribose polymerase 1 (PARP-1) in the human intracranial ruptured and unruptured aneurysm walls. Methods Consecutive patients with intracranial aneurysm treated with craniotomy clipping surgery in Drum Tower Hospital, Nanjing University School of Medicine (n = 1) and General Hospital of Eastern War Zone (n = 12) from January 2014 to September 2018 were enrolled retrospectively. Seven of them were ruptured aneurysms and 6 were unruptured aneurysms. The expression of PARP-1 in aneurysm walls was detected by immunohistochemistry. Results Immunohistochemistry staining showed that the positive expression of PARP-1 was brown-yellow and mainly located in nuclei; in the unruptured aneurysm walls,the number of PARP-1 positive cells was small, the distribution was sparse,and it expressed in the whole layer of the aneurysm wall;in the ruptured aneurysm walls,PARP-1 positive cells were densely distributed in the outer membrane of the vessel walls. Statistical analysis showed that the positive expression of PARP-1 in the ruptured aneurysm walls was higher than that in the unruptured aneurysm walls. The difference was statistically significant(160 ± 19 vs. 56 ± 14,1 = 4. 291, P < 0. 01) . Conclusion The expression of PARP-1 in the ruptured aneurysm walls is significantly higher than that in the unruptured aneurysms,which may play a role in the rupture of intracranial aneurysms.

Mutation analysis of FBN1 gene in a child with Marfan syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutations of fibrillin-1 (FBN1) gene in a child with Marfan syndrome (MFS) and explore its molecular pathogenesis.</p><p><b>METHODS</b>The 66 exons of the FBN1 gene were analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the structural and functional changes at the protein level.</p><p><b>RESULTS</b>A novel heterozygous mutation c.3998 G>A (p.Cys1333Tyr) was found in exon 32 in the child. The same mutation was not found among his unaffected family members and 683 healthy controls. Multiple sequence alignment showed that this novel mutation was located in a highly conserved region of the FBN1 protein across various species and may induce structural change to a functional domain.</p><p><b>CONCLUSION</b>The novel c.3998G>A (p.Cys1333Tyr) mutation of the FBN1 gene probably predisposed the MFS in the child. Above finding has enriched the spectrum of FBN1 mutations.</p>

Association of ZP4 gene polymorphism with primary open-angle glaucoma in an ethnic Chinese population from Sichuan province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of single nucleotide polymorphisms (SNP) rs547984, rs540782, rs693421 and rs2499601 of Zona Pellucida Glycoprotein 4 (ZP4) gene with primary open-angle glaucoma (POAG) among ethnic Han Chinese from Sichuan Province.</p><p><b>METHODS</b>A dye terminator-based SNaPshot method was used to genotype 336 patients with POAG and 768 healthy controls.</p><p><b>RESULTS</b>No significant difference was detected in allelic frequencies of rs547984, rs540782, rs693421 and rs2499601 between the two groups (P>0.05). Haplotypic analysis showed a significant difference in G-G-A-G haplotype formed by the 4 SNPs between the POAG and the control groups (P<0.05).</p><p><b>CONCLUSION</b>ZP4 gene SNPs rs547984, rs540782, rs693421, rs2499601 are not associated with POAG among ethnic Hans from Sichuan.</p>

Relationship Between Ambulatory Pulse Pressure, Pulse Pressure Index and Coronary Artery Disease in Hypertension Patients / 中国循环杂志

Objective: To investigate the relationship between 24-hour ambulatory pulse pressure (24hPP), 24-hour ambulatory pulse pressure index (24hPPI), night-time ambulatory pulse pressure index (NPPI) and coronary artery disease (CAD) occurrence in hypertension patients. Methods: A total of 305 subjects received ambulatory blood pressure monitoring (ABPM) in our hospital from 2016-05 to 2016-07 were enrolled. Base on ABPM information, 24hPP, 24hPPI and NPPI were calculated to analyze their relationship to CAD occurrence. 24hPP was defined by 24-hour mean systolic blood pressure (24hSBP) minus 24hDBP, 24hPPI by the ratio of 24hPP/24hSBP and NPPI by the ratio of night (22:00-6:00) PP/SBP. Results: There were 222/305 (72.8%) subjects with hypertension. Compared with normotension subjects, hypertension patients had increased 24hPP: (49.0±11.6) mmHg vs (42.2±7.4) mmHg, P<0.001, 24hPPI: (0.39±0.06) vs (0.37±0.05), P=0.004 and NPPI: (0.40±0.07) vs. (0.38±0.06), P=0.009 respectively. 116/222 (52.3%) hypertension patients suffered from CAD. Compared with non-CAD patients, CAD patients presented elevated 24hPP: (50.9±12.2) mmHg vs (47.0±10.6) mmHg, P=0.013, 24hPPI: (0.41±0.07) vs. (0.38±0.06), P<0.001 and NPPI: (0.42±0.07) vs. (0.38±0.06), P<0.001 respectively. Among 83/305 (27.2%) normotension subjects, the above indexes were similar between CAD patients and non-CAD subjects. Logistic regression analysis demonstrated that with adjusted age, gender, body mass index (BMI) and antihypertensive medication, 24hPPI [OR=1.95, 95% CI 1.11-3.44, P=0.020] and NPPI [OR=2.21, 95% CI 1.28-3.82, P<0.01] were related to CAD occurrence. ROC curve analysis showed that 24hPPI and NPPI were superior to 24hPP for CAD screening and prediction in hypertension patients. Conclusion: 24hPPI and NPPI were closely related to CAD occurrence in hypertension patients, they were both helpful for CAD screening and prediction in hypertension patients.

Advance in molecular genetic research on X-linked syndromic hearing impairment / 中华医学遗传学杂志

In addition to hearing impairment, syndromic hearing impairment is often accompanied by disorders of urinary, skeletal, muscular, nervous, and ocular systems. Genetic factors have shown to play an important role in the pathogenesis of deafness. Mutations of X-linked genes may cause syndromic hearing impairment. Gene mapping, linkage analysis and next-generation sequencing may facilitate delineation of the pathogenesis of X-linked syndromic hearing impairment. This article reviews recent progress in molecular genetic research on X-linked syndromic hearing impairment, which may shed light for the diagnosis and treatment of these diseases.

Effect of targeted monitoring and comprehensive intervention on reducing catheter-associated urinary tract infection in patients in non-intensive care unit / 中国感染控制杂志

Objective To evaluate the effect of targeted monitoring and comprehensive intervention measures on reducing the occurrence of catheter-associated urinary tract infection(CAUTI)in patients in non-intensive care unit(Non-ICU).Methods In quarter 4 of 2015,patients with indwelling urinary catheter in clinical departments were conducted a baseline survey(before intervention),risk factors for CAUTI in patients were analyzed,targeted monitoring programmes and comprehensive intervention measures were initiated in 2016(after intervention),incidence of CAUTI before and after intervention was compared.Results After taking intervention measures,hand hygiene compliance rate increased from 78.51%in quarter 4 of 2015 to 92.99%in quarter 3 of 2016 and 90.73%in quarter 4 of 2016(x2=7.342,3.998,respectively,both P<0.05),the correct disposal rate of patients' urinary catheterization system increased from 72.83%in quarter 4 of 2015 to 95.44%in quarter 4 of 2016(x2=30.267,P<0.05).A total of 12 067 patients with indwelling urinary catheter were monitored,incidence of CAUTI dropped from 1.03%(24/23 313)in quarter 4 of 2015(before intervention)to 0.53%(14/26 595)in quarter 4 of 2016(after intervention),difference was statistically significant(x2=4.126,P=0.042).Conclusion Improving the quality of urinary catheterization system in patients with indwelling catheter through targeted monitoring can effectively reduce the incidence of CAUTI in patients in Non-ICU.

Advance in molecular genetic research on primary congenital glaucoma / 中华医学遗传学杂志

Primary congenital glaucoma (PCG) is one of the major diseases causing blindness in children, but its pathogenesis has remained unclear. Genetic factors play an important role in the pathogenesis of PCG. Molecular genetics of candidate genes such as CYP1B1, MYOC, LTBP2 and FOXC1 has so far been explored, but no disease-causing gene has been identified. Molecular genetic research on PCG including candidate gene screening and research strategies are reviewed here.

Progress of molecular genetics research on rheumatoid arthritis / 中华医学遗传学杂志

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disorder that principally attacks flexible joints and synovia. The precise pathogenesis of RA remains unclear, and genetic factors probably play an important role in its etiology. In addition to genes from human leukocyte antigen (HLA) region, such as HLA-DRB, genes from non-HLA region, such as TIM-3, PTPN22, TRAF1/C5, STAT4, CCR5, PADI4 and FCGR2A may also contribute to its susceptibility. The advance in molecular genetics research on RA is reviewed here.

Association between LOXL1 gene polymorphisms and primary open angle glaucoma in Sichuan population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate association between the lysyl oxidase-like 1 (LOXL1) gene single nucleotide polymorphism (SNP) and primary open-angle glaucoma (POAG) in Sichuan population.</p><p><b>METHODS</b>In this study,416 subjects with primary open-angle glaucoma and 997 normal controls were recruited.Three reported LOXL1 tag SNPs (rs1048661,rs3825942 and rs2165241) were genotyped by SNaPshot method.</p><p><b>RESULTS</b>The study showed that the genotypes of LOXL1 rs1048661,rs3825942 and rs2165241 between POAG and control groups were not statistically significant (OR=1.085, 95%CI 0.92-1.28, P=0.578 for rs1048661; OR=1.059, 95%CI 0.82-1.37, P=0.846 for rs3825942; OR=1.006, 95%CI 0.77-1.32, P=0.966 for rs2165241, respectively). There were no significant difference in allele frequency distribution of LOXL1 rs1048661、rs3825942 and rs2165241 between POAG and normal controls (P=0.322, P=0.660, P=0.965).</p><p><b>CONCLUSION</b>The results from the present study do not indicate the association of LOXL1 SNPs (rs1048661, rs3825942 and rs2165241) with POAG in Sichuan population.</p>

I148M polymorphism of PNPLA3 gene affects cell cycle of hepatoma carcinoma cell Huh-7 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the cell cycle of Huh-7 cells affected by I148M polymorphism of PNPLA3 gene and the possible mechanisms.</p><p><b>METHODS</b>Huh-7 cells which could respectively overexpress PNPLA3 wild type and I148M variant were cultured and Huh-7 cells with zero load plasmids were used as matched control, Flow cytometry was conducted to detect the cell cycles of these 3 type of Huh-7 cells and western blot and realtime fluorescence quantitative PCR were applied to investigate the expression of regulatory factors (Cyclin D1 and p53) of cell cycle. t-test was used in statistical analysis.</p><p><b>RESULTS</b>Cell cycle phase distribution was presented by the proportion of cells in each phases (%), compared with the control group, the cell cycle phase distribution (G1 phase 59.27 ± 0.15, G2/M phase 24.23 ± 0.31, S phases 16.50 ± 0.26) had no differences in wild type group (G1 phase 58.53 ± 0.35, G2/M phase 24.87 ± 0.60, S phases 16.60 ± 0.26; Probability value less than 0.05). While between variant type group and wild type group, G1 phase was significantly decreased (variant type group G phase 38.37 ± 0.21, Probability value less than 0.05), S phase and G2/M phase were increased (variant type group S phase 27.47 ± 0.35, P less than 0.05; G2/M phase 34.17 ± 0.15, P less than 0.05), respectively. compared with control group, the relative expression of P53 mRNA in variant type group was significantly upregulated (control group 1.06 ± 0.41, variant type group 6.54 ± 0.34; Probability value less than 0.05) and there was no statistical significance in wild type group (1.66 ± 0.30, P more than 0.05); Cyclin D1 expression showed no statistical significance in any of these three groups, control group 1.00 ± 0.10, wild type group 1.06 ± 0.03, variant type group, 1.11 ± 0.04; P > 0.05).</p><p><b>CONCLUSION</b>I148M polymorphism of PNPLA3 gene affects cell cycles of Huh-7 cells via up-regulatating P53.</p>

Association between the PNPLA3 I148M polymorphism and chronic hepatitis B in a Qingdao Han Chinese population / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the association between the PNPLA3 rs738409 polymorphism and chronic hepatitis B (CH[B) in a Han Chinese population residing in Qingdao.</p><p><b>METHODS</b>Peripheral blood samples were collected from 185 CHB patients and 164 healthy controls and subjected to polymerase chain reaction (PCR) and DNA sequencing to determine the PNPLA3 genotypes. The relative risk of the rs738409 polymorphism for CHB was estimated by calculating the odds ratio (OR) and 95% confidence interval.</p><p><b>RESULTS</b>The rs738409 G allele frequency was significantly different between the CHB and control groups (31.9% vs.21.9% respectively, P less than 0.05). Compared to he rs738409 C allele, the G allele was associated with an increased risk of developing CHB (OR =1.67, 95% CI:1.18-2.34, P =0.003). Logistic regression model analysis, with adjustment for confounding factors, indicated that carriers of the PNPLA3 rs738409 GG + GC genotype had increased risk of CHB than carriers of the CC genotype (OR =1.76 ,95% CI:1.14-2.71, P =0.011).</p><p><b>CONCLUSION</b>Qingdao Han Chinese who are carriers of the rs738409 G allele are at increased risk of CHB.</p>

Relationship Between Blood Pressure Variability and Ambulatory Arterial Stiffness Index in Both Normal Subjects and Hypertensive Patients / 中国循环杂志

Objective: To investigate the relationship between blood pressure variability and ambulatory arterial stiffness index (AASI) in both normal subjects and hypertensive patients. Methods: A total of 280 consecutive subjects without antihypertensive medication were studied. All subjects received ambulatory blood pressure monitoring (ABPM) and AASI was calculated as 1 minus the regression slope of diastolic blood pressure value vs systolic blood pressure value according to ABPM recording. Results: ① There were 161 subjects with male gender, 138 patients with hypertension, and the average age was (50.4 ± 13.3) years.②Pearson analysis indicated that AASI was related to age (r=0.272, P0.05 respectively.④Multiple linear regression analysis demonstrated that with adjusted age, gender, BMI and blood pressure, AASI was independently related to 24-hour mean pulse pressure (β=0.003, P Conclusion:AASI is closely related to blood pressure variability, it’s a comprehensive index for arterial stiffness and blood pressure variability.

Analysis of COL9A2 gene mutations in a Chinese Han population with pathological myopia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the mutation of COL9A2 gene and investigate the molecular pathogenesis of pathological myopia in a Han Chinese population.</p><p><b>METHODS</b>Mutation in the coding region of the COL9A2 gene was screened by Sanger sequencing in 200 subjects with pathological myopia and 200 normal controls. The detected variants were genotyped by SNaPshot method in another 200 myopic cases and 200 normal controls.</p><p><b>RESULTS</b>Sanger sequencing has failed to detect the reported D281fs frameshift mutation in the 200 cases. A novel variant, c.143G>C heterozygous missense mutation in exon 2, was identified in a myopic subject, and another novel variant, c.884G>A heterozygous missense mutation in exon 17, was found in another case. Neither was found in normal controls. One SNP (rs2228564) was detected in the coding region of the COL9A2 gene, but there was no significant difference in its allelic frequencies between the two groups (P> 0.05). Genotyping of the remainder 200 cases and 200 controls by SNaPshot method has found a c.143G>C in 1 case and c.884G>A in 2 cases, though no significant difference between the two groups was detected (P> 0.05).</p><p><b>CONCLUSION</b>The D281fs frameshift mutation in the COL9A2 gene is not associated with pathological myopia in the studied Han Chinese population. Two novel mutations, c.143G>C in exon 2 and c.884G>A in exon 17 of the COL9A2 gene, may contribute to the development of pathological myopia.</p>

Analysis and carrier screening for copy numbers of SMN and NAIP genes in children with spinal muscular atrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of copy number variations of SMN1, SMN2, NAIP, GTF2H2 and H4F5 genes with clinical classification of spinal muscular atrophy in children, and determine the copy number of the SMN gene among pregnant women. A carrier screening was also performed in Sichuan province.</p><p><b>METHODS</b>The copy number variations of the above genes among 53 confirmed SMA patients were determined with MLPA technique. The copy number variations were analyzed by the Fisher's exact test. Deletion of exon 7 in the SMN1 gene was screened with denaturing high performance liquid chromatography (DHPLC) for 427 pregnant women.</p><p><b>RESULTS</b>Among the 53 cases of type I, II, and III SMA patients, the rate of homozygous deletion of both exons 7 and 8 of the SMN1 gene were 100%, 94.44% and 87.50%, respectively, whereas those of homozygous deletion of exon 7 of SMN1 gene were 0, 5.56%, and 12.50%, respectively. The patients with 1, 2, 3, and 4 copies of exon 7 of the SMN2 gene were 11.32%, 67.92%, 13.21% and 7.55%, respectively. The patients with 0, 1, and 2 copies of exon 5 of NAIP gene were 11.32%, 62.26%, and 26.42%, respectively. No deletion was detected in GTF2H2 or H4F5 genes. The heterozygous loss rate of exon 7 in SMN gene in the pregnant women population of Sichuan region was approximately 2.11%.</p><p><b>CONCLUSION</b>Copy number variations of SMN2 and NAIP genes in patients are related to SMA clinical types (P < 0.05). In contrast, there was no relationship between SMA clinical types and deletion of exons 7 and 8 in the SMN1 gene (P > 0.05). Analysis of copy number change in SMN1 gene can assist SMA carrier screening. However, when the general population without SMA family history is screened for disease-causing genes, it should be noted that the type "2+0" carriers may affect the screening result, and the result should be interpreted with caution.</p>

Model Package Inserts of OTC Traditional Chinese Medicines:Problems and Suggestions / 中国药房

OBJECTIVE:To standardize model package inserts of OTC traditional Chinese medicines(TCM).METHODS:4 341 model package inserts of OTC TCM retrieved from the website of State Food and Drug Administration(SFDA)were given a meta-analysis.RESULTS:Through an incomplete statistical analysis,7 major problems were found in the model package inserts,for example,the kinds of TCM that were of the same generic name were different in functions and indications.CONCLUSIONS:There are many problems in the model package inserts of OTC TCM,which call for the efforts of the concerned department to facilitate the standardization of the model package inserts of OTC TCM.

Analysis of Drug-Resistance of Acinetobacter Baumannii Producing AmpC Enzyme / 中国医师杂志

Objective To investigate the drug-resistance and distribution of 142 strains acinetobacter baumannii.Methods Drug-resistance test of acinetobacter baumannii strains was observed in 13 kinds of antibiotics.The drug sensitivity tests was performed by the method of Kirby-Bauer paper-diffusion with the standard of NCCLS.AmpC enzyme was examined by cefoxitin three dimension test and PCR amplification of ampC structure gene were studied.Results The main sources of specimen were sputum,wound secretion,urine and blood.The respiratory tract was a major site to the development of acinetobacter baumannii.Acinetobacter baumannii strain emerged mostly in the intensive care unites.The drug resistance to cefotaxime,ceftriaxome and aztreonam were high.PCR amplification showed that of 142 acinetobacter baumannii strains,23 strains had ampC structure gene which accounted for 16 2% total strains.The drug resistance of acinetobacter baumannii producing AmpC enzyme were significantly higher than those of non-producing AmpC.The best choice of treatment was imipenem.Conclusions Acinetobacter baumannii have higher multiple-antibiotic resistance,the finding prompting us to project prospective control strategies.